Peak Intracavernous Pressure Research Articles

Lacosamide alleviates bilateral cavernous nerve injury-induced erectile dysfunction in the rat model by ameliorating pathological changes in the corpus cavernosum.

Bilateral cavernous nerve injury-related erectile dysfunction (BCNI-ED) shows a limited response to type 5 phosphodiesterase inhibitors. Furthermore, lacosamide (LCM) can alleviate peripheral neuropathy. To explore whether LCM can improve the erectile response after BCNI, we randomly divided 30 young Sprague-Dawley rats into three groups (n = 10 per group), namely, the sham operation, 0.9% normal saline-treated (BCNI + 0.9% NS), and LCM-treated BCNI (BCNI + LCM) groups. LCM was injected intraperitoneally at a dose of 90 mg/kg/day for 7 consecutive days. Erectile function was assessed by measuring the ratio of peak intracavernous pressure (ICP) to mean arterial pressure (MAP), and tissues were harvested for transmission electron microscopy, immunofluorescence, Masson's trichrome staining, TUNEL staining, and Western blot analysis. The BCNI + 0.9% NS group showed reduced ICP/MAP ratio (0.93 ± 0.04 vs. 0.44 ± 0.05, P < 0.0001). An increased proportion of TUNEL-positive cells (0.04 ± 0.01 vs 0.87 ± 0.03, P < 0.0001) and a decreased smooth muscle/collagen ratio (0.44 ± 0.01 vs. 0.33 ± 0.01, P < 0.001) were observed in the BCNI + 0.9% NS compared with the sham group. Administration of LCM significantly restored the ICP/MAP ratio (0.44 ± 0.05 vs. 0.74 ± 0.05, P < 0.001) and decreased the proportion of TUNEL positive cells (0.87 ± 0.03 vs. 0.60 ± 0.04, P < 0.0001) in the corpus cavernosum following BCNI. The ratio of smooth muscle to collagen (0.43 ± 0.01vs. 0.33 ± 0.01, P < 0.01) and expression of α-SMA (P < 0.0001) in the BCNI + LCM group significantly increased compared with BCNI + 0.9% NS group, indicating alleviation of fibrosis. Apoptotic markers, including Bax/Bcl-2 (P < 0.01) and Caspase-3 (P < 0.0001) in the BCNI + LCM group was significantly lower than that in the BCNI + 0.9% NS group. LCM treatment partially upregulated the expression of vWF and eNOS in cavernous tissue in rats subjected to BCNI (P < 0.05). Increases in S100-β and nNOS expression in the major pelvic ganglion (MPG) were observed after LCM administration. In summary, LCM can recover erectile function in BCNI-ED rat model by suppressing corporal apoptosis and fibrosis, and protecting the cavernous nerve.

Restoration of erectile function by suppression of corporal apoptosis and oxidative stress with losartan in aged rats with erectile dysfunction.

The prevalence of erectile dysfunction (ED) increases progressively with age, but its potential pathophysiology has not been fully demonstrated. Hence, this article was aimed to identify the functional and morphological characterization of the corpus cavernosum in aged rats and to evaluate the effects of the Angiotensin II type 1 receptor antagonist losartan on age-related ED (AED). A total of 40 young and aged Sprague Dawley rats were randomly divided into four groups (n=10 per group): young rats as normal controls (YNC) group; aged rats with normal erectile function (ANC) group; aged rats with ED (AED) group; and a losartan-treated AED (AED+Losartan) group. The treated group received losartan (30mg/kg) once daily oral gavage for 4weeks. Erectile function was measured by the ratio of peak intracavernous pressure (ICP)/mean arterial pressure (MAP), and relevant tissues were harvested for transmission electron microscopy, Immunohistochemistry, Masson's trichrome staining, TUNEL, caspase-3 activity assay and Western blot. The AED group exhibited decreases in erectile response and increases in the role of apoptosis, fibrosis as well as oxidative stress, compared with the control groups. After daily administration of losartan for four weeks, it could slightly restore erectile function and significantly attenuate corporal apoptosis, fibrosis, and oxidative stress of AED. However, the result was still not comparable with that of the control groups. Moreover, the expression levels of p-Bad/Bad and p-AKT/AKT were significantly lower, whereas the expression levels of Bax/Bcl-2, Nrf2/Keap-1, Fibronectin, HO-1, and caspase-3 activity were significantly higher in the AED groups and while losartan could significantly attenuate these changes of AED, it was still not comparable with that of the control groups. Our results indicated that administration of losartan not merely restored erectile function, but also significantly prevented corporal apoptosis and oxidative stress in AED by suppressing the Akt/Bad/Bax/caspase-3 and Nrf2/Keap-1 pathways.

Hydro-Jet Dissection of the Cavernous Nerves Preserves Erection Function in a Radical Prostatectomy Animal Model.

BackgroundPostoperative erectile dysfunction (ED) remains a prevalent consequence of radical prostatectomy (RP) that significantly impacts patient quality of life. Water-jet technology is widely used for dissection in neurosurgical procedures but novel to urologic surgery.AimTo establish the impact of hydro-jet dissection (HJD) of the cavernous nerves (CN) on postoperative erectile function in an animal model of RP-induced ED.Methods32 male Sprague-Dawley rats were randomized to 4 groups: Sham surgery (n = 8), bilateral HJD of CN (n = 8), blunt CN injury (n = 8), or stretch CN injury (n = 8). After 4 weeks, erectile function was assessed by measuring intracavernous pressure (ICP), and penile tissues were harvested for immunohistologic studies.Main Outcome MeasureThe peak ICP and the area under the curve were calculated for each group. Immunohistologic studies were performed for α-smooth muscle actin and neuronal nitric oxide synthase on cross-sections of penile tissue.ResultsRats in the HJD group demonstrate a significantly higher mean peak ICP and area under the curve compared with both CN injury groups (P = .001). Postoperative erectile function in the HJD group returned to baseline function. Preservation of α-smooth muscle actin and neuronal nitric oxide synthase was observed in the HJD group compared with the other surgical trauma groups.Clinical ImplicationsHydro-jet dissection used in an RP animal model maintains erectile function and offers a potential benefit that warrants further human studies.Strengths & LimitationsThis is a novel animal study comparing a new technology to established CN dissection techniques. This study uses an animal model, which may not completely translate to post-RP ED in humans.ConclusionHydro-jet dissection of the CN during RP in an animal model is associated with significantly better postoperative erectile function when compared with other CN injury. Clinical studies are needed to further investigate the putative benefit of HJD on erectile function in patients undergoing RP.Campbell JD, Alenezi H, DeYoung LX, et al. Hydrojet Dissection of the Cavernous Nerves Preserves Erection Function in a Radical Prostatectomy Animal Model. Sex Med 2019;7:104–110.

Beneficial Effect of Berberis amurensis Rupr. on Penile Erection.

To investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments. The ex vivo study used corpus cavernosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP), blood pressure, mean arterial pressure (MAP), and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats. Preconstricted with phenylephrine (PE) in isolated endotheliumintact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA, P<0.01), a nonselective K+ channel blocker, 4-aminopyridine (4-AP, P<0.01), a voltage-dependent K+ channel blocker, and charybdotoxin (P<0.01), a large and intermediate conductance Ca2+ sensitive-K+ channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently. BAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca2+ sensitive-K+ (BKCa and IKCa) channels in the corpus cavernosum.

The herbal formula KH-204 is protective against erectile dysfunction by minimizing oxidative stress and improving lipid profiles in a rat model of erectile dysfunction induced by hypercholesterolaemia

BackgroundHypercholesterolaemia (HC) is a major risk factor for ischemic heart disease and is also known to be a risk factor for erectile dysfunction (ED). ED caused by HC is thought to be related to HC-induced oxidative stress damage in the vascular endothelium and erectile tissue. KH-204 is an herbal formula with a strong antioxidant effect. We evaluated the effects of KH-204 on erectile function in a rat model of HC-induced ED.MethodsMale Sprague-Dawley rats (6 weeks old) were divided into normal control, high-fat and cholesterol diet (HFC), and HFC with KH-204 treatment (HFC + KH) groups (n = 12 each). Normal control group rats were fed normal chow diet. HFC and HFC + KH group rats were fed high-fat and cholesterol diets and treated with or without daily oral doses of KH-204 for 12 weeks. Subsequently, intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured, and lipid profiles, expression of endothelial (eNOS) and neuronal (nNOS) nitric oxide synthase, oxidative stress (8-hydroxy-2-deoxyguanosine), and ratio of smooth muscle cells and collagen fibres were evaluated in the serum and corpora tissue.ResultsCompared to the HFC group, the HFC + KH group showed statistically significant increases in peak ICP and ICP/MAP ratio, expression of eNOS and nNOS, and ratio of smooth muscle cells and collagen fibres (p < 0.05). The HFC + KH group also showed statistically significant decreases in oxidative stress (p < 0.05). Further the lipid profiles of this group were ameliorated compared to those of the HFC group (p < 0.05).ConclusionsThe current study shows that the antioxidant and hypolipidemic effects of KH-204 are effective in ameliorating ED by restoring endothelial dysfunction and suggests that KH-204 may be a potential therapeutic agent for ED by correcting the fundamental cause of ED.

B Cell Lymphoma-2-Modified Bone Marrow-Derived Mesenchymal Stem Cells Transplantation for the Treatment of Diabetes Mellitus-Induced Erectile Dysfunction in a Rat Model

Objective: The study aimed to explore the effects of B cell lymphoma-2 (Bcl-2)-modified bone marrow-derived mesenchymal stem cells (BMSCs) transplantation for the treatment of diabetes mellitus-induced erectile dysfunction (DMED) in a rat model. Methods: The DMED rat model was successfully established. Thirty-six DMED rats were assigned into the Bcl-2-BMSCs, null-BMSCs, BMSCs and phosphate buffered saline (PBS) groups. Meanwhile, 9 normal rats injected with PBS were taken as the normal control group. Results: In the Bcl-2-BMSCs group, the average times of erection, rate of erection, peak intra-cavernous pressure (ICP) and peak ICP/mean arterial pressure were higher than those in the null-BMSCs, BMSCs and PBS groups, but were lower than those in the normal control group. In the Bcl-2-BMSCs group, capillary vessels and Bcl-2 mRNA and protein expressions were similar to those in the normal control group, while they were higher than those in other groups. Conclusion: These findings indicate that Bcl-2-modified BMSC transplantation could improve erectile function in DMED rats.

Antioxidative mechanism of Lycium barbarum polysaccharides promotes repair and regeneration following cavernous nerve injury.

Polysaccharides extracted from Lycium barbarum exhibit antioxidant properties. We hypothesized that these polysaccharides resist oxidative stress-induced neuronal damage following cavernous nerve injury. In this study, rat models were intragastrically administered Lycium barbarum polysaccharides for 2 weeks at 1, 7, and 14 days after cavernous nerve injury. Serum superoxide dismutase and glutathione peroxidase activities significantly increased at 1 and 2 weeks post-injury. Serum malondialdehyde levels decreased at 2 and 4 weeks. At 12 weeks, peak intracavernous pressure, the number of myelinated axons and nicotinamide adenine dinucleotide phosphate-diaphorase-positive nerve fibers, levels of phospho-endothelial nitric oxide synthase protein and 3-nitrotyrosine were higher in rats administered at 1 day post-injury compared with rats administered at 7 and 14 days post-injury. These findings suggest that application of Lycium barbarum polysaccharides following cavernous nerve crush injury effectively promotes nerve regeneration and erectile functional recovery. This neuroregenerative effect was most effective in rats orally administered Lycium barbarum polysaccharides at 1 day after cavernous nerve crush injury.

AB73. Effect of human tissue kallikrein 1(hKLK1) on penile erectile function in the aged rat

Human tissue kallikrein1 (hKLK1), as a pleiotropic agent in cardiovascular system, plays an important role in vasodilation, endothelial cell protection, anti-tissue fibrosis, etc. However, wheather hKLK1 has impact on erectile function is still unknown. This study was aim to explore the effect and the potential mechanisms of hKLK1 on age-related erectile dysfunction (ED) with the transgenic Sprague-Dawley (SD) rats harboring hKLK1 gene (TGR(hKLK1)). Both of male wild type SD rats and TGR(hKLK1) were fed to 4 month old and 27 month old and divided into four groups: young wild type rats (yWTR) as the control group; young TGR(hKLK1) (yTGR) group; aged wild type rats (aWTR) group and aged TGR(hKLK1) (aTGR) group. The existence of hKLK1 gene in each rat was identified at genome DNA, mRNA and protein level. The ratio of peak intracavernous pressure (ICP) to systemic mean arterial pressure (MAP) at various voltages of electrical stimulation to the cavernous nerve (CN) were measured to evaluate the erectile function of rats in all groups. Then, the expression of endothelial nitric oxide synthase (eNOS), phospho-eNOS(Ser1177), phospho-eNOS(Thr495), inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), cyclooxygenase-2 (COX2) and prostaglandin I synthase (PTGIS) in corpus cavernosum (CC) were measured by real-time reverse transcriptase-PCR and/ or western blot. Afterwards, we assayed NO production and the nitric oxide synthase (NOS) activity in CC. The concentration of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) in CC were also examined by enzyme-linked immunosorbent assay (ELISA). Furthermore, the transforming growth factor β1 (TGFβ1) expression and the ratio of smooth muscle to collagen by masson’s trichrome staining within CC were analyzed to evaluate the degree of penile tissue fibrosis. Lastly, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was conducted to calculate the apoptosis index (AI) of cells in CC. All TGR (hKLK1) carried and expressed hKLK1 gene while wild type rats negatively contained it. No conspicuous diversity was found between yWTR and yTGR groups at all the rest of the tests. The peak ICP/MAP ratio of aWTR group was considerably decreased compared with the control group, but the erectile function was greatly improved in aTGR group relative to aWTR group at voltages of 2.5V, 5.0V and 7.5V. When compared to control group, the expression of eNOS, phospho-eNOS(Ser1177) and COX2 in CC were decreased while phospho-eNOS(Thr495) was increased significantly in aWTR group, but these changes were obviously restored in aTGR group. No difference of iNOS, nNOS and PTGIS protein content was found between four groups. The NO level and NOS activity in aTGR was markedly higher than that in aWTR, although it was still lower than yWTR. In accord with the above results, the cGMP and cAMP concentration were improved dramatically in CC of aTGR. Moreover, hKLK1 could prevent the increase of TGFβ1 mRNA and protein expression and smooth muscle/collagen ratio in CC of aWTR. Meanwhile, hKLK1 could attenuate the cell apoptosis in CC of aged rat. In summary, our results suggest that hKLK1 may improve penile erectile function in the aged rat via activating eNOS/NO/cGMP and COX2/cAMP pathways and anti-tissue fibrosis as well as anti-apoptosis effect.

Study on penile corpus cavernosum relaxation induced by Berberis amurensis Rupr (1075.10)

Study on Penile corpus cavernosum relaxationinduced by Berberis amurensis RuprRui Tan 1, 2, , Hye Yoom Kim 1,2, Kyung Woo Cho2, Dae Gill Kang 1,2, and Ho Sub Lee 1,2*1College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570‐749, Republic of Korea; 2Hanbang Body‐fluid Research Center, Wonkwang University, Shinyong‐dong, Iksan, Jeonbuk, 570‐749, Republic of KoreaThe aim of the present study is to investigate whether a methanol extract of Berberis amurensis Rupr (BAR) augments penile erection. Preconstracted with phenylephrine (PE) in isolated endothelium‐intact rabbit corpus cavernosum, BAR relaxed penile smooth muscle in a dose‐dependent manner, which was inhibited by pretreatment with NG‐nitro‐L‐arginine methyl ester (L‐NAME), a nitric oxide synthase inhibitor, and 1H‐[1,2,4]‐oxadiazole‐[4,3‐α]‐quinoxalin‐1‐one (ODQ), a soluble guanylyl cyclase (sGC) inhibitor. BAR‐induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA), a nonselective K+ channel blocker for BKCa, IKCa and SKCa, and charybdotoxin, iberiotoxin, apamin, a selective Ca2+ sensitive K+ channel inhibitor, respectively. BAR increased cGMP levels of the corpus cavernosum in a concentration‐dependent manner. In addition, BAR caused increase of peak intracavernous pressure (ICP), ICP/MAP ratio and area under the carve (AUC) in a dose dependent manner in SD rats. Taken together, these results suggest that BAR augments penile erection via NO/cGMP system and Ca2+ sensitive‐K+ Channel in corpus cavernosum.

MP47-09 HKLK1 IMPROVES THE ERECTILE FUNCTION IN AGED RATS BY ENHANCING ENOS AND INOS EXPRESSON AND ANTI-TISSUE FIBROSIS EFFECT

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2014MP47-09 HKLK1 IMPROVES THE ERECTILE FUNCTION IN AGED RATS BY ENHANCING ENOS AND INOS EXPRESSON AND ANTI-TISSUE FIBROSIS EFFECT Yang Luan, Tao Wang, Li Zhuan, Yan Zhang, Ya-Jun Ruan, Shao-Gang Wang, Ji-Hong Liu, and Zhang-Qun Ye Yang LuanYang Luan More articles by this author , Tao WangTao Wang More articles by this author , Li ZhuanLi Zhuan More articles by this author , Yan ZhangYan Zhang More articles by this author , Ya-Jun RuanYa-Jun Ruan More articles by this author , Shao-Gang WangShao-Gang Wang More articles by this author , Ji-Hong LiuJi-Hong Liu More articles by this author , and Zhang-Qun YeZhang-Qun Ye More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1462AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Age is the most common risk factor for erectile dysfunction (ED). Human tissue kallikrein1 (hKLK1), as a pleiotropic agent, plays an important role in vasodilation, endothelial cell protection, anti-tissue fibrosis, etc. We aim to explore the effect and preliminarily test the mechanisms of hKLK1 on age-related erectile dysfunction with transgenic rats harboring hKLK1gene (TGR(hKLK1). Methods Four groups of adult male Sprague-Dawley rats were involved in this study: 1) young wild type rats (yWTR, 4 months, n = 10) as control group; 2) young TGR(hKLK1) (yTGR, 4 months, n = 10) group; 3) aged wild type rats (aWTR, 27 months, n = 10) group; 4) aged TGR (hKLK1) (aTGR, 27 months, n = 26) group. Extraction of genome DNA followed by conventional polymerase chain reaction (PCR) and real-time PCR after reverse transcription-PCR of tissue RNA were performed to identify the existence of hKLK1gene. The ratio of peak intracavernous pressure (ICP) to systemic mean arterial pressure (MAP) were measured at various voltages of electrical stimulation to the cavernous nerve (CN) to evaluate the erectile function of rats in each group. The eNOS and iNOS expression in penis were detected by real-time PCR. The ratios of smooth muscle to collagen and apoptosis within the corporal tissue were analyzed by masson's trichrome staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively. Results All TGR (hKLK1) carried hKLK1gene while wild type rats negtively contained it. No conspicuous diversity was found between yWTR and yTGR groups at electrostimulation to CN, real-time PCR, masson's trichrome staining and TUNEL assays. The ICP/MAP ratio of aWTR group was decreased compared with the control group (P<0.05), but the erectile function was greatly improved in aTGR group relative to aWTR group (P<0.05, respectively) and reached the level of control group at all kinds of voltages of 2.5v, 5.0v and 7.5v. The expression of mRNA for eNOS in aTGR was markedly higher than that in aWTR (P<0.05), although it was still lower than yWTR (P<0.01). Moreover, the iNOS mRNA expression in aTGR was obviously increased than that in aWTR and yWTR (P<0.05 of both). The reduction of the smooth muscle/collagen in aWTR, relative to yWTR, was significantly attenuated in aTGR (P<0.01). Meanwhile, the apoptosis data showed the same tendency towards the results of masson's trichrome staining (P<0.001). Conclusions Our results suggest that hKLK1 may improve ED in aged rats via promoting eNOS and iNOS expression and anti-tissue fibosis as well as anti-apoptosis effect. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e521 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Yang Luan More articles by this author Tao Wang More articles by this author Li Zhuan More articles by this author Yan Zhang More articles by this author Ya-Jun Ruan More articles by this author Shao-Gang Wang More articles by this author Ji-Hong Liu More articles by this author Zhang-Qun Ye More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The effect of Lycium barbarum polysaccharides on erectile function recovery in a rat model of cavernous nerve injury

This study aimed to investigate the effect of Lycium barbarum polysaccharides (LBP) on erectile function recovery in a rat model of cavernous nerves (CN) injury. Adult male Sprague-Dawley rats were randomly divided into 3 groups: ten rats underwent sham operation (sham group), ten underwent bilateral CN crush injury (injured control group) and the other ten underwent bilateral CN crush injury with an oral administration of LBP for 12 weeks (LBP application group). Oxidative stress was evaluated by malondialdehyde (MDA) level, super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in serum. Erectile function was assessed by CN electro-stimulation and CN regeneration was evaluated by toluidine blue staining at 12 weeks. After 12 weeks, the peak intracavernous pressure (ICP) and peak ICP per mean arterial pressure in the LBP application group were significantly higher than those in the injured control group, although lower than the sham group. The number of myelinated axons of CN in the LBP application group was more than that in the injured control group but fewer than the sham group. The results demonstrate that the application of LBP after CN crush injury promotes nerve regeneration and erectile function recovery. Key words: Erectile dysfunction, Lycium barbarum polysaccharides, oxidative stress, nerve regeneration.

SaRNA Guided iNOS Up-Regulation Improves Erectile Function of Diabetic Rats

Promoter targeted saRNAs mediate sequence specific up-regulation of gene expression. We explored the therapeutic effect of RNA activation mediated iNOS gene activation on improving erectile function in a rat model of diabetes mellitus. An optimal saRNA sequence specific for iNOS promoter was cloned into an adenoviral vector, resulting in AdU6/shiNOS and AdU6/shControl. The corresponding viruses were used to transduce cultured rat cavernous smooth muscle cells. Streptozotocin induced diabetes models were established in rats and used to test the effects of intracavernous delivery of iNOS saRNA viruses on erectile function. iNOS expression in the cavernous smooth muscle cells or penile tissue of treated rats was assessed by reverse transcriptase-polymerase chain reaction and Western blot. Cyclic guanosine monophosphate was analyzed by enzyme-linked immunosorbent assay. Intracavernous pressure in response to cavernous nerve stimulation was measured using a data acquisition system on post-injection days 1, 3, 5, 7, 10 and 14. Adenovirus mediated expression of iNOS saRNA caused sustained up-regulation of iNOS in cavernous smooth muscle cells. Intracavernous injection of AdU6/shiNOS activated iNOS expression in vivo and significantly increased peak intracavernous pressure in streptozotocin induced diabetic rats via nitric oxide/intracellular cyclic guanosine monophosphate activation. Results show that saRNA mediated iNOS over expression in the penis can restore erectile function in streptozocin diabetic rats via the nitric oxide-cyclic guanosine monophosphate pathway.

1113 COMPARISON OF THE EFFECT ON INTRACAVERNOUS PRESSURE INCREASE AFTER ELECTRICAL STIMULATION OF CAVERNOUS NERVE BETWEEN DAILY AND WEEKLY ADMINISTRATION OF SILDENAFIL IN THE RAT

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research1 Apr 20111113 COMPARISON OF THE EFFECT ON INTRACAVERNOUS PRESSURE INCREASE AFTER ELECTRICAL STIMULATION OF CAVERNOUS NERVE BETWEEN DAILY AND WEEKLY ADMINISTRATION OF SILDENAFIL IN THE RAT Kuang-Kuo Chen Kuang-Kuo ChenKuang-Kuo Chen Taipei, Taiwan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.710AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Once daily or on-demand use of phosphodiesterase-5 inhibitors has been suggested to improve erectile function, especially for penile rehabilitation after radical prostatectomy. The objective of this study was to compare the effect of daily or weekly (on-demand) administration of sildenafil on intracavernous pressure (ICP) increase after electrical stimulation (ES) of cavernous nerve (CN) in the rat. METHODS Male adult Sprague-Dawley rats were used. Five groups of experiments were designed: 1) group 1: without administration of sildenafil, 2) group 2: daily oro-gastric administration (OGA) of sildenafil 0.13 mg for one week, 3) group 3: OGA of sildenafil 0.5 mg at the end of one week, 4) group 4: daily OGA of sildenafil 0.13 mg for 4 weeks, and 5) group 5: OGA of sildenafil 0.5 mg every week for 4 weeks. A 26-gauge needle was inserted into the corpus cavernosum to measure the ICP. The CN was electrically stimulated with parameters (5, 7.5, 10 V, 20 Hz, 2 ms, 1 minute) on the 7th day for the group 2 and group 3 rats, and on the 28th day for the group 4 and group 5 rats. The amount of ICP increase was calculated by subtracting resting ICP from peak ICP. RESULTS There was a significant increase of ICP from resting 12.5 ±1.4 mmHg to a peak 52.7 ±6.8 mmHg after ES of CN with parameter 10V in group 1 rats. A significant increase of ICP from resting 7.7 ±1.2 mmHg to a peak 75.3 ±3.5 mmHg after ES of CN with 10V was also noted in group 2 rats. There was a significant increase of ICP from resting 7.0 ±1.6 mmHg to a peak at 72.0 ±5.1 mmHg after ES of CN with 10V in group 3 rats. A significant increase of ICP from resting 8.7 ±2.6 mmHg to a peak at 67.2 ± 4.3 mmHg after ES of CN with 10V was also noted in group 4 rats. There was a significant increase of ICP from resting 8.8 ±2.5 mmHg to a peak at 66.3 ±5.3 mmHg after ES of CN in group 5 rats. The amount of ICP increase was 40.2 ±5.6 mmHg, 68.5 ±3.9 mmHg, 65.0 ±4.7 mmHg, 58.5 ±3.2 mmHg and 57.5 ±4.7 mmHg in group 1, 2, 3, 4, and 5, respectively. There was a significantly greater amount of ICP increase in groups 2, 3, 4, and 5 rats as compared with group 1 rats. No significant difference of amount of ICP increase was noted among group 2, 3, 4, and 5 rats. CONCLUSIONS The results suggest that there is a significant greater amount of ICP increase after ES of CN in the rats with daily or weekly oral administration of sildenafil than those without sildenafil administration. However, no significant difference of the ICP increase after ES of CN is noted among daily and weekly oral administration of sildenafil for up to 4 weeks in the rat. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e447 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kuang-Kuo Chen Taipei, Taiwan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

KTP Laser Nerve Sparing Radical Prostatectomy: Comparison of Ultrasonic and Cold Scissor Dissection on Cavernous Nerve Function

Energy sources used during nerve sparing radical prostatectomy are known to compromise cavernous nerve function. Lasers offer the potential for accurate dissection while minimizing collateral injury to delicate neural structures. We evaluated cavernous nerve function following KTP laser dissection and compared outcomes to those of ultrasonic shears and cold scissor dissection. Laparoscopic unilateral neurovascular bundle mobilization was performed in 36 survival dogs using a KTP laser, ultrasonic shears and an athermal technique with cold scissors and clips in 12 each. Peak intracavernous pressure upon cavernous nerve stimulation, expressed as a percent of mean arterial pressure, was measured acutely and at 1 month. Thermal spread from the KTP laser and ultrasonic shears was assessed histologically ex vivo in harvested peritoneum. Median peak intracavernous pressure as a percent of mean arterial pressure was similar immediately and 1 month after laser and athermal dissection, and significantly decreased after dissection with ultrasonic shears. Acute peak intracavernous pressure as a percent of mean arterial pressure was 53%, 96% and 98% for ultrasonic shears, laser and the athermal technique, respectively (laser vs athermal p = 0.51, ultrasonic shears vs laser p <0.001 and ultrasonic shears vs athermal p <0.001). Chronic peak intracavernous pressure as a percent of mean arterial pressure was 56%, 98% and 100% for ultrasonic shears, laser and the athermal technique, respectively (laser vs athermal p = 0.38, ultrasonic shears vs laser p = 0.016 and ultrasonic shears vs athermal p = 0.013). The median depth of acute laser injury was 600 microm compared to 1.2 mm for ultrasonic shear dissection and 450 microm crush injury due to the athermal technique. Thermography revealed less collateral thermal spread from the laser than from the ultrasonic shears (median greater than 60C thermal spread 1.07 vs 6.42 mm, p <0.01). The KTP laser was comparable to the athermal technique and superior to the ultrasonic shears for preserving cavernous nerve function.

Anatomical and Electrophysiological Assessment of the Canine Periprostatic Neurovascular Anatomy: Perspectives as a Nerve Sparing Radical Prostatectomy Model

Although the dog is often used as a radical prostatectomy model, precise descriptions of canine prostate and neurovascular bundle anatomy are lacking. We describe canine prostate and neurovascular bundle anatomical and electrophysiological characteristics. The canine prostate and pelvic neurovascular structures were dissected in 6 canine cadavers and 12 anesthetized dogs. Pelvic plexus branches were stimulated using a CaverMap probe and peak intracavernous pressure responses were recorded as a percent of mean arterial pressure. The canine pelvic plexus lies 5 to 10 mm lateral to the prostate. It is supplied by the hypogastric nerve cranially and the pelvic nerve laterally. The neurovascular bundles course distal from the pelvic plexus along the posterolateral aspect of the prostate, including a dominant cavernous nerve along its lateral aspect. CaverMap stimulation of the efferent branches of the pelvic plexus confirmed their roles in tumescence. Histology revealed extensive neurovascular tissue along the posterolateral aspect of the prostate beneath the periprostatic fascia. Notable differences to human anatomy were the absence of seminal vesicles, the lateral positions of the pelvic plexus, the dominant cavernous nerve and the circumferential urethral distribution of the cavernous nerves. Canine neurovascular anatomy resembles that of humans and it is a suitable model in which to assess prostatectomy related erectile dysfunction. However, there are key differences in neurovascular relationships that must be considered when the canine prostate is used as a radical prostatectomy model.

Gene Transfer of Endothelial Nitric Oxide Synthase Partially Restores Nitric Oxide Synthesis and Erectile Function in Streptozotocin Diabetic Rats

We determined whether adenoviral gene transfer of endothelial nitric oxide synthase (eNOS) to the penis of streptozotocin induced diabetic rats could improve the impaired erectile response. Two experimental groups of animals were transfected with adenoviruses, including streptozotocin (Sigma Chemical Company, St. Louis, Missouri) diabetic rats with AdCMVbetagal and streptozotocin diabetic rats with AdCMVeNOS. At 1 to 2 days after transfection these study animals underwent cavernous nerve stimulation to assess erectile function and their responses were compared with those of age matched control rats. In control and transfected streptozotocin diabetic rats eNOS and neuronal NOS (nNOS) were examined by Western blot analysis. Constitutive and inducible NOS activities were evaluated in the presence and absence of calcium by L-arginine to L-citrulline conversion and nitrate plus nitrite levels were measured. In control and streptozotocin diabetic penes beta-galactosidase activity and localization were determined. After transfection with AdCMVbetagal beta-galactosidase was localized to the endothelium and smooth muscle cells of the streptozotocin diabetic rat penis. Streptozotocin diabetic rats had a significant decrease in erectile function, as determined by peak and total intracavernous pressure (area under the curve) after cavernous nerve stimulation compared with control rats. Streptozotocin diabetic rats transfected with AdCMVeNOS had peak intracavernous pressure and area under the curve similar to those in control animals. This change in erectile function was a result of eNOS over expression with an increase in eNOS protein expression and constitutive NOS activity as well as an increase in nitric oxide biosynthesis, as reflected by an increase in cavernous nitrate plus nitrite formation. There was no change in nNOS protein expression or calcium independent conversion of NOS (inducible NOS activity). Adenoviral gene transfer of eNOS significantly increased peak and total intracavernous pressure to cavernous nerve stimulation in streptozotocin diabetic rats to a value similar to the response observed in control rats. Our results suggest that eNOS contributes significantly to the physiology of penile erection. These data demonstrate that in vivo adenoviral gene transfer of eNOS can physiologically improve erectile function in the streptozotocin diabetic rat.

Nitric Oxide Independent Activation of Guanylate Cyclase by YC-1 Causes Erectile Responses in the Rat

Activation of soluble guanylate cyclase with a subsequent increase in intracellular levels of cyclic guanosine monophosphate is necessary for normal erection. In vascular tissue 3(5'-hydroxymethyl-2'-furyl-1-benzyl indazole (YC-1) (Abbott Laboratories, North Chicago, Illinois) has been shown to stimulate soluble guanylate cyclase independent of nitric oxide. We studied whether YC-1 modulates erectile responses in the rat. The effects of YC-1 given intracavernously or intraperitoneally on intracavernous pressure were investigated in rats. Functional effects of YC-1 on neuronal and endothelial nitric oxide relaxations were studied in 3 x 10(-6) M. 1-noradrenaline contracted preparations of rat isolated corpus cavernosum. Intracavernous YC-1 (10 micromol. kg.-1) produced erectile responses with a mean intracavernous pressure plus or minus standard error of mean of 81 +/- 17 cm. water (p <0.001) and a mean duration of 7.1 +/- 3.3 minutes (p <0.001). YC-1 (10 micromol. kg.-1) given intraperitoneally also increased the amplitude and duration of erectile responses to cavernous nerve stimulation. Mean peak intracavernous pressure increased from 63 +/- 6 to 10(2) +/- 16 cm. water (p <0.05). Erections induced by a submaximal dose of 25 microg. kg.-1 apomorphine s.c. increased in number after 10 micromol. kg.-1 YC-1 intraperitoneally (p <0.05). In vitro nerve induced relaxant responses were enhanced by increasing concentrations of YC-1. Relaxations at 20 Hz. were increased from a mean of 9% +/- 5% to 52% +/- 5% at a YC-1 concentration of 10(-5) M. (p <0.001). At this concentration carbachol induced relaxations were enhanced from a mean of 19% +/- 3% to 40% +/- 9% (p <0.05). YC-1 can evoke erectile responses when given intracavernously and it enhances erections induced by cavernous nerve stimulation and apomorphine when given systemically. In vitro YC-1 enhances electrically evoked relaxations in rat corpus cavernosum. YC-1 represents an interesting pharmacological principle that may be useful for treating erectile dysfunction.

??-MELANOCYTE STIMULATING HORMONE AND OXYTOCIN INDUCED PENILE ERECTIONS, AND INTRACAVERNOUS PRESSURE INCREASES IN THE RAT

alpha-Melanocyte stimulating hormone (alpha-MSH; Fluka Chemie AG, Geneva, Switzerland) and oxytocin induce erection in rats after intracerebroventricular administration. We studied possible interactions of alpha-melanocyte stimulating hormone with mechanisms pertaining to oxytocin or nitric oxide. We used 78 anesthetized male Sprague-Dawley rats. Catheters were implanted in the lateral cerebral ventricle or into the subarachnoid space at L6 to S1. Intracavernous pressure was documented and arterial blood pressure was directly measured. Intracerebroventricular alpha-MSH (3 microg.) produced a mean of 2.6 +/- 0.6 erectile responses (p <0.05) with a mean duration of 3.4 +/- 1.1 minutes (p <0.05). Mean peak intracavernous pressure was 114 +/- 8 cm. water. An intracerebroventricular dose of 100 microg. N-nitro-L-arginine-methyl ester HCl (Sigma Chemical Co., St. Louis, Missouri) given in intracerebroventricular fashion abolished alpha-MSH induced erectile responses, whereas intracerebroventricular administration of 500 ng. of the oxytocin receptor antagonist l-deamino, 2-D-Tyr(Oet), 4-Thr, 8-Orn-OT (Ferring AB, Malmö, Sweden) had no effect. Intracerebroventricular oxytocin (30 ng.) induced a mean of 3.2 +/- 0.9 erectile responses (p <0.05) with a mean peak intracavernous pressure of 81 +/- 8 cm. water and a mean duration of 3.3 +/- 1.1 minutes. Intrathecal alpha-MSH (3 microg.) did not produce any erectile responses, whereas a mean of 5.7 +/- 0.9 responses (p <0.001) with a mean peak intracavernous pressure of 142 +/- 8 cm. water and mean duration of 5.0 +/- 1.3 minutes was obtained with 30 ng. oxytocin intrathecally. Responses induced by intrathecal oxytocin were abolished by 100 microg. N-nitro-L-arginine-methyl ester HCl intrathecally. We confirmed by monitoring intracavernous pressure and blood pressure that supraspinal erectile responses induced by alpha-melanocyte stimulating hormone involve effects mediated by nitric oxide but are independent of oxytocinergic mechanisms. At the spinal level oxytocin produces erectile responses involving nitric oxide. alpha-Melanocyte stimulating hormone does not seem to have a spinal site of action.

α-MELANOCYTE STIMULATING HORMONE AND OXYTOCIN INDUCED PENILE ERECTIONS, AND INTRACAVERNOUS PRESSURE INCREASES IN THE RAT

alpha-Melanocyte stimulating hormone (alpha-MSH; Fluka Chemie AG, Geneva, Switzerland) and oxytocin induce erection in rats after intracerebroventricular administration. We studied possible interactions of alpha-melanocyte stimulating hormone with mechanisms pertaining to oxytocin or nitric oxide. We used 78 anesthetized male Sprague-Dawley rats. Catheters were implanted in the lateral cerebral ventricle or into the subarachnoid space at L6 to S1. Intracavernous pressure was documented and arterial blood pressure was directly measured. Intracerebroventricular alpha-MSH (3 microg.) produced a mean of 2.6 +/- 0.6 erectile responses (p <0.05) with a mean duration of 3.4 +/- 1.1 minutes (p <0.05). Mean peak intracavernous pressure was 114 +/- 8 cm. water. An intracerebroventricular dose of 100 microg. N-nitro-L-arginine-methyl ester HCl (Sigma Chemical Co., St. Louis, Missouri) given in intracerebroventricular fashion abolished alpha-MSH induced erectile responses, whereas intracerebroventricular administration of 500 ng. of the oxytocin receptor antagonist l-deamino, 2-D-Tyr(Oet), 4-Thr, 8-Orn-OT (Ferring AB, Malmö, Sweden) had no effect. Intracerebroventricular oxytocin (30 ng.) induced a mean of 3.2 +/- 0.9 erectile responses (p <0.05) with a mean peak intracavernous pressure of 81 +/- 8 cm. water and a mean duration of 3.3 +/- 1.1 minutes. Intrathecal alpha-MSH (3 microg.) did not produce any erectile responses, whereas a mean of 5.7 +/- 0.9 responses (p <0.001) with a mean peak intracavernous pressure of 142 +/- 8 cm. water and mean duration of 5.0 +/- 1.3 minutes was obtained with 30 ng. oxytocin intrathecally. Responses induced by intrathecal oxytocin were abolished by 100 microg. N-nitro-L-arginine-methyl ester HCl intrathecally. We confirmed by monitoring intracavernous pressure and blood pressure that supraspinal erectile responses induced by alpha-melanocyte stimulating hormone involve effects mediated by nitric oxide but are independent of oxytocinergic mechanisms. At the spinal level oxytocin produces erectile responses involving nitric oxide. alpha-Melanocyte stimulating hormone does not seem to have a spinal site of action.

THE EFFECT OF SILDENAFIL ON APOMORPHINE-EVOKED INCREASES IN INTRACAVERNOUS PRESSURE IN THE AWAKE RAT

The aim of this study was to develop a quantitative, awake animal model to investigate the effect of sildenafil on centrally-evoked erectile activity. Intracavernous pressures were recorded in awake, male Sprague Dawley rats after administration of apomorphine (100 or 250 microg./kg. subcutaneously). Sildenafil (100 microg./kg. intravenously) was then given 10 min. after a second dose of apomorphine. The time to first response, duration of response, and peak intracavernous pressure and area under the response, were measured before and after sildenafil. Apomorphine produced rhythmic increases in intracavernous pressure. The pressure increase consisted of two components. The amplitude of the first, tonic response was 58 +/- 3 mm. Hg, and a superimposed, burst-like increase in pressure elevated this further to 81 +/- 6 mm. Hg. Bilateral transection of the pudendal nerves abolished the burstlike pressure changes; bilateral transection of the cavernous nerves prevented both responses. The duration of the apomorphine-induced increase in intracavernous pressure was significantly (p = 0.003) prolonged by sildenafil (100 microg./kg.) from 37 +/- 4 to 62 +/- 11 s (n = 6). The overall intracavernous pressure response to apomorphine (100 microg./kg.), measured as the area under the curve, was significantly (p = 0.003) increased by sildenafil (100 microg./kg.) from 67 +/- 8 to 142 +/- 31 units (n = 6). N-nitro-L-arginine methyl ester (40 mg./kg. intravenously) prevented the apomorphine-induced responses. Monitoring intracavernous pressures in the awake rat represents a simple model to evaluate the effect of drugs on erectile function. Using this model we have shown that apomorphine elicits a rise in intracavernous pressure that can be prolonged by sildenafil. These results suggest that there may be a role for the combination of apomorphine and sildenafil in the management of erectile dysfunction.