Significant Vasodilator Effect Research Articles

Preliminary Characterization of the Vasorelaxant Effect of Thymus atlanticus (Ball) Roussine Using Optical Methods.

Thymus atlanticus (Ball) Roussine is a Moroccan endemic thyme species that is traditionally used as an aromatic and medicinal plant. Several studies have demonstrated its pharmacological significance and therapeutic value. The current study aimed to assess the vasorelaxant effect of the aqueous extract of this species. The contractility of isolated rat aortas was investigated using the multi-well organ bath technique. This method was adapted and validated in our experimental conditions using epinephrine and hydralazine as vasoconstrictive and vasodilator agents, respectively. The application of 10 μM epinephrine induced a clear vasoconstriction of the aorta rings (Lumen reduction = 31.8±0.4%). However, hydralazine induced a dose-dependent relaxation with an EC50 value of 6.1±1.2 mM. For the aqueous extract of T. atlanticus, the aortic rings were precontracted with epinephrine, and then increasing concentrations (0.125-1 mg/mL) of this extract were added cumulatively. The results have indicated T. atlanticus extract to have a significant vasodilatory effect in a dose-dependent manner (EC50 = 0.52±0.03 mg/mL). The findings provide preliminary evidence of the vasorelaxant effect of the aqueous extract of T. atlanticus using a low-cost optical approach. However, the cellular and molecular mechanisms underlying this effect have yet to be revealed.

The hydroxamic acid derivative YPX-C-05 alleviates hypertension and vascular dysfunction through the PI3K/Akt/eNOS pathway

Hypertension is a prevalent cardiovascular disease characterized by elevated blood pressure and increased vascular resistance. HDAC inhibitors have emerged as potential therapeutic agents due to their ability to modulate gene expression and cellular processes. YPX-C-05, a novel hydroxamic acid-based HDAC inhibitor, shows promise in its vasodilatory effects and potential targets for hypertension treatment. In this study, we aimed to elucidate the mechanisms underlying YPX-C-05's vasodilatory effects and explore its therapeutic potential in hypertension. To determine the ex vivo vasodilatory effects of YPX-C-05, isolated aortic rings precontracted with phenylephrine were used. We assessed YPX-C-05's inhibitory effects on HDACs and its impact on histone H4 deacetylation levels in endothelial cells. Network pharmacology analysis was employed to predict putative targets of YPX-C-05 for hypertension treatment. To investigate the involvement of the PI3K/Akt/eNOS pathway, we employed enzyme-linked immunosorbent assay and to assess the levels of NO, ET-1, BH2, and BH4 in human umbilical vein endothelial cells. And we also analyzed the mRNA expression of eNOS and ET-1. Furthermore, Western blotting was conducted to quantify the phosphorylated and total Akt and eNOS levels in human umbilical vein endothelial cell lysates following treatment with YPX-C-05. In order to elucidate the vasodilatory mechanism of YPX-C-05, we employed pharmacological inhibitors for evaluation purposes. Furthermore, we evaluated the chronic antihypertensive effects of YPX-C-05 on N-omega-nitro-L-arginine-induced hypertensive mice in an in vivo model. Vascular remodeling was assessed through histological analysis. Our findings demonstrated that YPX-C-05 exerts significant vasodilatory effects in isolated aortic rings precontracted with phenylephrine. Furthermore, YPX-C-05 exhibited inhibitory effects on HDACs and increased histone H4 acetylation in endothelial cells. Network pharmacology analysis predicted YPX-C-05 might activate endothelial eNOS via PI3K/Akt signaling pathway. Inhibition of the PI3K/Akt/eNOS pathway attenuated the vasodilatory effects of YPX-C-05, as evidenced by reduced levels of phosphorylated Akt and eNOS in human umbilical vein endothelial cell lysates. The chronic administration of YPX-C-05 in N-omega-nitro-L-arginine-induced hypertensive mice resulted in significant antihypertensive effects. Histological analysis demonstrated a reduction in vascular remodeling, further supporting the therapeutic potential of YPX-C-05 in hypertension. This study demonstrates for the first time that the novel hydroxamic acid-based HDAC inhibitor YPX-C-05 produces significant antihypertensive and vasodilatory effects through the PI3K/Akt/eNOS pathway. Our findings support the developing prospect of YPX-C-05 as a novel antihypertensive drug.

Investigating the Cardiovascular Benefits of Dapagliflozin: Vasodilatory Effect on Isolated Rat Coronary Arteries

Dapagliflozin, a sodium–glucose co-transporter 2 (SGLT2) inhibitor, is an antidiabetic medication that reduces blood glucose. Although it is well known that dapagliflozin has additional benefits beyond glycemic control, such as reducing blood pressure and lowering the risk of cardiovascular events, no sufficient research data are available on the direct effect of dapagliflozin on cardiovascular function. Thus, in this study, we investigated the direct vascular effect of dapagliflozin on isolated rat coronary arteries. The left descending coronary arteries of 13-week-old male Sprague Dawley rats were cut into segments 2–3 mm long and mounted in a multi-wire myography system to measure isometric tension. Dapagliflozin effectively reduced blood vessel constriction induced by U-46619 (500 nM) in coronary arteries regardless of the endothelium. Treatment with an eNOS inhibitor (L-NNA, 100 μM), sGC inhibitor (ODQ, 5 μM), or COX inhibitor (indomethacin, 3 μM) did not affect the vasodilation induced by dapagliflozin. The application of a Ca2+-activated K+ channel (KCa) blocker (TEA, 2 mM), voltage-dependent K+ channel (KV) blocker (4-AP, 2 mM), ATP-sensitive K+ channel blocker (KATP) glibenclamide (3 μM), and inward-rectifier K+ channel (KIR) blocker (BaCl2, 30 μM) did not affect the dapagliflozin-induced vasodilation either. The treatment with dapagliflozin decreased contractile responses induced by the addition of Ca2+, which suggested that the extracellular Ca2+ influx was inhibited by dapagliflozin. Treatment with dapagliflozin decreased the phosphorylation level of the 20 kDa myosin light chain (MLC20) in vascular smooth muscle cells. In the present study, we found that dapagliflozin has a significant vasodilatory effect on rat coronary arteries. Our findings suggest a novel pharmacologic approach for the treatment of cardiovascular diseases in diabetic patients through the modulation of Ca2+ homeostasis via dapagliflozin administration.

The Cardiorenal Effects of Piper amalago Are Mediated by the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway and the Voltage-Dependent Potassium Channels.

Piper amalago L. is used in Brazilian traditional medicine to treat inflammation, chest pain, and anxiety. This study aimed to investigate the safety and the renal and cardiovascular effects of the volatile oil (VO) and the aqueous (AE) and hydroalcoholic (HE) extracts from P. amalago. The gas chromatography-mass spectrometry analyses identified 47 compounds in the VO, with β-cyclogermacrene, spathulenol, β-phellandrene, and α-pinene standing out. Among the 47 compounds also found in AE and HE by liquid chromatography-mass spectrometry, glycosylated flavones, organic acids, amino acids, and amides were highlighted. Some examples of these compounds are methoxy-methylenedioxy cis-cinnamoyl pyrrolidine, methoxy-methylenedioxy trans-cinnamoyl pyrrolidine, and cyclobutene-2,4-bis-(1,3-benzodioxol-5-methoxy-6-yl)-1,3-dicarboxapyrrolidide. The acute toxicity experiments were conducted on female rats (n = 5). The cardiorenal assays (n = 8) and evaluations of vasodilatory effects on the mesenteric vascular bed (n = 5) were conducted on male rats. In either extract or VO, there were no mortality or changes in relative weights or histopathological analysis of the organs. Urinary volume and renal electrolyte excretion were elevated significantly during repeated dose 7-day treatment with different preparations from P. amalago. None of the preparations induced hypotension or changes in cardiac electrical activity. Only HE promoted significant vasodilatory effects in rats' isolated mesenteric vascular beds. These effects were completely abolished in the presence of L-NAME plus 4-aminopyridine. Therefore, P. amalago leaves are safe and present diuretic activity after acute and repeated dose administration over 7 days. Moreover, the HE induced significant vasodilator response in rats' mesenteric vascular beds by NO/cGMP pathway and voltage-dependent K+ channels activation.

Ezetimibe Induces Vasodilation in Rat Mesenteric Resistance Arteries through Inhibition of Extracellular Ca2+ Influx.

Ezetimibe is a lipid-lowering agent that selectively inhibits cholesterol absorption by binding to the Niemann-Pick C1-like 1 (NPC1L1) protein. Although it is well known that administration of ezetimibe in hypercholesterolemia patients reduces the risk of cardiovascular events through attenuation of atherosclerosis, studies on the direct effect of ezetimibe on vascular function are not sufficient. The aim of the present study was to investigate the vascular effects of ezetimibe in rat mesenteric arteries. In the present study, 12-week-old male Sprague Dawley rats were used. After the rats were sacrificed, the second branches of the mesenteric arteries were isolated and cut into 2-3 mm segments and mounted in a multi-wire myography system to measure isometric tension. Ezetimibe reduced vasoconstriction induced by U46619 (500 nM) in endothelium-intact and endothelium-denuded arteries. Ezetimibe-induced vasodilation was not affected by the endothelial nitric oxide synthase (eNOS) inhibitor Nω-Nitro-L-arginine (L-NNA, 300 μM) or the non-selective potassium channel blocker, tetraethylammonium (TEA, 10 mM). Moreover, ezetimibe also completely blocked the contraction induced by an increase in external calcium concentration. Ezetimibe significantly reduced vascular contraction induced by L-type Ca2+ channel activator (Bay K 8644, 30 nM). Treatment with ezetimibe decreased the phosphorylation level of 20 kDa myosin light chain (MLC20) in vascular smooth muscle cells. In the present study, we found that ezetimibe has a significant vasodilatory effect in rat mesenteric resistance arteries. These results suggest that ezetimibe may have beneficial cardiovascular effects beyond its cholesterol-lowering properties.

Manipulation of Nitric Oxide Levels via a Modified Hydroxyethyl Starch Molecule

IntroductionAlthough the improving effect of nitric oxide (NO) donors has experimentally been demonstrated in shock, there are still no NO donor medications clinically available. Thiol-nitrosothiol-hydroxyethyl starch (S-NO-HES) is a novel molecule consisting of NO coupled to a thiolated derivative of hydroxyethyl starch (HES). It was aimed to assess the ability of S-NO-HES to serve as an NO donor under a variety of in vitro simulated physiologic conditions, which might be the first step to qualify this molecule as a novel type of NO donor-fluid. MethodsWe studied the effect of temperature on NO-releasing properties of S-NO-HES in blood, at 34°C, 37°C, and 41°C. Ascorbic acid (Asc) and amylase were also tested in a medium environment. In addition, we evaluated the activity of S-NO-HES in the isolated aortic ring and Langendorff-perfused heart setup. ResultsThe NO release property of S-NO-HES was found at any temperature. Asc led to a significant increase in the production of NO compared to S-NO-HES incubation (P < 0.05). The addition of amylase together with Asc to the medium further increased the release of NO (P < 0.05). S-NO-HES exerted significant vasodilatory effects on phenylephrine precontracted aortic rings that were dose-dependent (P < 0.01). Furthermore, S-NO-HES significantly increased the heart rate and additionally reduced the duration of the cardiac action potential, as indicated by a reduction of QTc-B values (P < 0.01). ConclusionsWe demonstrated for the first time that the S-NO-HES molecule exhibited its NO-releasing effects. The effectiveness of this new NO donor to substitute NO deficiency under septic conditions or in other indications needs to be studied.

Vasodilatory effects of a variety of positive allosteric modulators of GABAA receptors on rat thoracic aorta

Different subtypes of GABAA (gamma-aminobutyric acid A) receptors, through their specific regional and cellular localization, are involved in the manifestation of various functions, both at the central and peripheral levels. We hypothesized that various non-neuronal GABAA receptors are expressed on blood vessels, through which positive allosteric modulators of GABAA receptors exhibit vasodilatory effects.This study involved two parts: one to determine the presence of α1-6 subunit GABAA receptor mRNAs in the rat thoracic aorta, and the other to determine the vasoactivity of the various selective and non-selective positive GABAA receptor modulators: zolpidem (α1-selective), XHe–III–074 (α4-selective), MP–III–022 (α5-selective), DK-I-56-1 (α6-selective), SH-I-048A and diazepam (non-selective).Reverse transcription-polymerase chain reaction (RT-PCR) analysis data demonstrated for the first time the expression of α1, α2, α3, α4 and α5 subunits in the rat thoracic aorta tissue. Tissue bath assays on isolated rat aortic rings revealed significant vasodilatory effects of diazepam, SH-I-048A, XHe–III–074, MP–III–022 and DK-I-56-1, all in terms of achieved relaxations (over 50% of relative tension decrease), as well as in terms of preventive effects on phenylephrine (PE) contraction. Diazepam was the most efficient ligand in the present study, while zolpidem showed the weakest vascular effects. In addition, diazepam-induced relaxations in the presence of antagonists PK11195 or bicuculline were significantly reduced (P < 0.001 and P < 0.05, respectively) at lower concentrations of diazepam (10−7 M and 3 × 10−7 M).The present work suggests that the observed vasoactivity is due to modulation of “vascular” GABAA receptors, which after further detailed research may provide a therapeutic target.

Dratanguticumides G and H, two new glucosides from Dracocephalum tanguticum Maxim relax vessels via NO pathway

Abstract Hypertension is one of the major sources of global incidence of cardiovascular diseases and one of the leading causes of global morbidity and mortality. It is necessary to search for natural products which have not adverse effects like many synthetic drugs as potential development agents for treating hypertension. Dracocephalum tanguticum Maxim, a perennial herb for Tibetan medicine in China, is widely used for the treatment of many diseases. In the present study, two new glucosides, Dratanguticumide G (1) and Dratanguticumide H (2), and seven known compounds (3-9) were isolated from D. tanguticum. The new structures were elucidated by spectroscopic data and the known ones were identified by comparison with spectroscopic data, physical and chemical data of reported references. The vasodilatory effects and the underlying mechanisms of the components of D. tanguticum on rat aortic rings were investigated. The result showed that the new compounds exhibited significant endothelium-dependent vasodilatory effects on the aortic rings, and the NO-dependent pathway and PI3K/AKT pathway might play a pivotal role in the vasodilatory effect, as did five of known compounds. Our findings firstly showed that some natural compounds of 95% ethanol extract of D. tanguticum had significant vasodilatory effects and could be the potential development agents for treating hypertension.

Mechanism underlying the vasodilation induced by diosmetin in porcine coronary artery

Diosmetin is a flavonoid present naturally in citrus fruit. Plants containing diosmetin have been reported to have anti-hypertensive and vasorelaxant effects. Therefore, experiments were carried out to study the effects of diosmetin in segments of the porcine coronary artery (PCA).PCA rings were mounted for isometric tension recording in isolated tissue baths and pre-contracted with the thromboxane A2 mimetic U46619 or KCl. Cumulative concentration response curves to diosmetin were then carried out in the presence or absence of inhibitors or activators of different signaling pathways. The effect on calcium channels was determined by investigating the effect of a single concentration of diosmetin (30 μM) on calcium-induced contractions or contractions to BAY K8644.Diosmetin caused a concentration-dependent relaxation after pre-contraction with U46619 or KCl, which was unaffected by removal of the endothelium. Tetraethylammonium (TEA), and 4-aminopyridine (4-AP), but not barium chloride, caused significant inhibition of the diosmetin-mediated vasorelaxation, indicating a role for potassium channels. Diosmetin inhibited calcium-induced contractions and contractions to the L-type calcium channel opener BAY K8644. Furthermore, diosmetin inhibited the contractions in response to caffeine, cyclopiazonic acid and ionomycin, indicating a general effect on calcium-induced contractions. Contractions in response to the protein kinase C (PKC) activator Phorbol 12-myristate 13-acetate (PMA) were also inhibited by diosmetin, suggesting that it may inhibit a calcium-activated PKC isoform.In summary, diosmetin produced significant vasodilatory effects. The data indicate a role for potassium channels as well as an effect on calcium-induced contractile pathways, possible through inhibition of PKC.

Furanoeremophilanes from Euryops arabicus alleviate metabolic syndrome-associated exaggerated vasoconstriction via direct vasodilatation

• Euryops arabicus alleviated MetS associated exaggerated vasoconstriction. • The chloroform fraction yielded eight furanoeremophilane derivatives. • All isolated compounds showed significant vasodilation activity. • Vasodilation activity may involve calcium channel blocking mechanism. Abstract Exaggerated vasoconstriction plays a critical role in the development of hypertension in metabolic syndrome (MetS). A crude methanolic extract of Euryops arabicus (EA) was found to alleviate MetS-associated exaggerated vasoconstriction. The methanolic extract of EA had a direct vasodilatory effect which might account for the alleviation of vasoconstriction. Bio-guided fractionation revealed that the chloroform fraction is responsible for this effect. The observed vasodilation was not affected by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), a nitric oxide (NO) synthase inhibitor or methylene blue (MB), a guanylate cyclase inhibitor, while it was increased by tetraethylammonium (TEA), a potassium channel blocker. In addition, the chloroform extract showed concentration-dependent inhibition of calcium-induced contraction. Chemical investigations of the chloroform fraction of EA revealed three new furanoeremophilanes, namely, 6-β-(2`-methyl-2`,3`-epoxy-propionyloxy)-10-α-H-9-oxofuranoeremophilane ( 4 ), 6- α -(2`-methyl, 2`,3`-epoxy-butyryloxy)-10-α-H-9-oxofuranoeremophilane ( 7 ), and 6-β-(2`-methyl, 2`,3`-epoxy-butyryloxy)-euryopsin ( 8 ), in addition to five other known metabolites, namely, 6-isovaleryloxy-euryopsin ( 1) , 6-isopropionyl-euryopsin (adenostylone) ( 2 ), 6-senecioyl-euryopsin-9-one ( 3 ) 6-β -(2`-methyl-2`,3`-epoxy-butyryloxy)-10-α-H-9-oxofuranoeremophilane ( 5 ), and euryopsonol-senecioate ( 6 ). All the isolated compounds showed significant vasodilatory effects that might involve calcium channel blocking, and compounds 7 and 8 were found to be the most bioactive ones.

Vasodilator Activity of Compounds Isolated from Plants Used in Mexican Traditional Medicine.

Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and flavonoids) isolated from 10 plants used in Mexican traditional medicine to determine whether they elicited vascular smooth muscle relaxation and, therefore, could represent novel anti-hypertension drug candidates. The vasorelaxant activity of these compounds was evaluated on the isolated rat aorta assay and the results obtained from this evaluation showed that three compounds induced a significant vasodilatory effect: meso-dihydroguaiaretic acid [half maximal effective concentration (EC50), 49.9 ± 11.2 µM; maximum effect (Emax), 99.8 ± 2.7%]; corosolic acid (EC50, 108.9 ± 6.7 µM; Emax, 96.4 ± 4.2%); and 5,8,4′-trihydroxy-3,7-dimethoxyflavone (EC50, 122.3 ± 7.6 µM; Emax, 99.5 ± 5.4%). Subsequently, involvement of the NO/cyclic guanosine monophosphate (cGMP) and H2S/ATP-sensitive potassium channel (KATP) pathways on the vasodilator activity of these compounds was assessed. The results derived from this analysis showed that the activation of both pathways contributes to the vasorelaxant effect of corosolic acid. On the other hand, the vasodilator effect of meso-dihydroguaiaretic acid and 5,8,4′-trihydroxy-3,7-dimethoxyflavone, partly involves stimulation of the NO/cGMP pathway. However, these compounds also showed an important endothelium-independent vasorelaxant effect, whose mechanism of action remains to be clarified. This study indicates that meso-dihydroguaiaretic acid, corosolic acid, and 5,8,4′-trihydroxy-3,7-dimethoxyflavone could be used as lead compounds for the synthesis of new derivatives with a higher potency to be developed as drugs for the prevention and treatment of cardiovascular diseases.

Nutritional value and volatile compounds of black cherry (Prunus serotina) seeds.

Prunus serotina (black cherry), commonly known in Mexico as capulín, is used in Mexican traditional medicine for the treatment of cardiovascular, respiratory, and gastrointestinal diseases. Particularly, P. serotina seeds, consumed in Mexico as snacks, are used for treating cough. In the present study, nutritional and volatile analyses of black cherry seeds were carried out to determine their nutraceutical potential. Proximate analysis indicated that P. serotina raw and toasted seeds contain mostly fat, followed by protein, fiber, carbohydrates, and ash. The potassium content in black cherry raw and toasted seeds is high, and their protein digestibility-corrected amino acid scores suggest that they might represent a complementary source of proteins. Solid phase microextraction and gas chromatography/flame ionization detection/mass spectrometry analysis allowed identification of 59 and 99 volatile compounds in the raw and toasted seeds, respectively. The major volatile compounds identified in raw and toasted seeds were 2,3-butanediol and benzaldehyde, which contribute to the flavor and odor of the toasted seeds. Moreover, it has been previously demonstrated that benzaldehyde possesses a significant vasodilator effect, therefore, the presence of this compound along with oleic, linoleic, and α-eleostearic fatty acids indicate that black cherry seeds consumption might have beneficial effects on the cardiovascular system.

Static magnetic field effect on microcirculation, direct versus baroreflex-mediated approach

We compared in conscious rabbits, sedated using pentobarbital intravenous (i.v.) infusion (5 mg kg− 1 h− 1), the effect of a static magnetic field (SMF), generated by Nd2–Fe14–B magnets, on microcirculation during its 40 min local exposure to the microvascular network in cutaneous tissue [20 sham exposure and 20 SMF (0.25 T) exposure runs] or to sinocarotid baroreceptors [14 sham exposure and 14 SMF (0.35 T) exposure runs]. Mean femoral artery blood pressure (BP), heart rate (HR), arterial baroreflex sensitivity (BRS), assessed from HR and BP responses to i.v. bolus of nitroprusside and phenylephrine, and microcirculatory blood flow, using microphotoelectric plethysmography (MPPG), were simultaneously monitored. SMF significantly increased microcirculation on a 17.8% in microvascular and on a 23.3% in baroreceptor exposure series. In baroreceptor exposure series, SMF significantly decreased BP, increased heart rate variability, BRS and sodium nitroprusside (NO-donor) i.v. bolus microcirculatory vasodilatory effect. These suggest augmentation of the arterial baroreflex capacity support NO-dependent vasodilation, by increased sensitivity of vessels to NO, to be a new physiological mechanism of BP buffering and microcirculatory control. A significant positive correlation was also found between increase in BRS and in MPPG (r = 0.66, p < 0.009), indicating baroreflex participation in the regulation of the microcirculation and its enhancement after SMF exposure. Both direct and baroreflex-mediated approaches demonstrate SMF significant vasodilatory effect with potential clinical implication in macro- and microcirculatory disorders.

Nitroso-redox balance in control of coronary vasomotor tone

Reactive oxygen species (ROS) are essential in vascular homeostasis but may contribute to vascular dysfunction when excessively produced. Superoxide anion (O(2)(·-)) can directly affect vascular tone by reacting with K(+) channels and indirectly by reacting with nitric oxide (NO), thereby scavenging NO and causing nitroso-redox imbalance. After myocardial infarction (MI), oxidative stress increases, favoring the imbalance and resulting in coronary vasoconstriction. Consequently, we hypothesized that ROS scavenging results in coronary vasodilation, particularly after MI, and is enhanced after inhibition of NO production. Chronically instrumented swine were studied at rest and during exercise before and after scavenging of ROS with N-(2-mercaptoproprionyl)-glycine (MPG, 20 mg/kg iv) in the presence or absence of prior inhibition of endothelial NO synthase (eNOS) with N(ω)-nitro-L-arginine (L-NNA, 20 mg/kg iv). In normal swine, MPG resulted in coronary vasodilation as evidenced by an increased coronary venous O(2) tension, and trends toward increased coronary venous O(2) saturation and decreased myocardial O(2) extraction. These effects were not altered by prior inhibition of eNOS. In MI swine, MPG showed a significant vasodilator effect, which surprisingly was abolished by prior inhibition of eNOS. Moreover, eNOS dimer/monomer ratio was decreased after MI, reflecting eNOS uncoupling. In conclusion, ROS exert a small coronary vasoconstrictor influence in normal swine, which does not involve scavenging of NO. This vasoconstrictor influence of ROS is slightly enhanced after MI. Since inhibition of eNOS abolished rather than augmented the vasoconstrictor influence of ROS in swine with MI, while eNOS dimer/monomer ratio was decreased, our data imply that uncoupled eNOS may be a significant source of O(2)(·-) after MI.

Tamsulosin Efficiency in Treatment of Benign Prostatic Hyperplasia Evaluated by Determining Bladder Weight

INTRODUCTION/GOAL: Bladder wall thickness and bladder mass are higher in patients with subvesical obstruction caused by benign prostate enlargement (BPE) in compensated stage of the disease. The goal of the study was to determine changes of bladder detrusor in patients suffering from benign prostatic hyperplasia (BPH) during tamsulosin treatment. The study was open, prospective and multi-centric. The material in this study was composed of 20 patients, aged > 45 years, with the present lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia, who had not been treated for the previous 3 months. The inclusive criteria also included the value of International Prostate Symptom Score (IPSS) > or = 8 points, post-void residual urine volume (PVR) < 100 ml and prostate specific antigen (PSA) < 4 ng/ml. After the end of the trials that were necessary for the introduction of the patients in the study, the patients started taking tamsulosin in a daily dosage of 0.4 mg, and the evaluation parameters during the research were measured at time intervals of 4, 12 and 24 weeks. The evaluation parameters were primary and secondary. The primary parameter included ultrasound estimated bladder weight (UEWB), while the secondary included determination of the blood pressure values (RR) and pulse frequency (PF), of total International Prostate Symptom Score (T-IPSS), a part of IPSS that related to the storage symptoms (I-PSS), a part that related to the voiding symptoms (O-IPSS), quality of life determination (IPSS-QoL), ultrasound estimation of prostate volume (VP) and the quantity of post-void residual urine volume (PVR), along with the determination of the number and strength of adverse reactions. During the introduction of the patients in the trial, the arithmetic mean of UEWB was 65 g, of PVR 43 ml, VP 35 ml, of total T-IPSS 15.6 points, of I-IPSS 6.9 points, of O-IPSS 8.7 points, and of IPSS-QoL 3.6 points. During the four-week, twelve-week and twenty-four-week checkups, the values were the following: the arithmetic mean of UEWB 36, 39 and 28 grams, of PVR 26, 29 and 21 ml, of T-IPSS 8.3, 6.4 and 5.0 points, of IPSS 3.8, 3.0 and 2.4 points, of O-IPSS 4.6, 3.4 and 2.6 points, of IPSS-QoL 1.7, 1.1 and 1.0 points and of VP 34 ml during the last control. The obtained results of this trial were processed by descriptive statistics (arithmetic mean and standard deviation) and analytical statistics by way of Student's t-test for dependant (paired) samples, with the comparison made between the obtained results with the zero checkup and four-week checkup, and subsequently the comparison between four-week and twelve-week checkup, twelve-week and twenty-four week checkup, and the zero checkup and the twenty-four week checkup. Adverse drug reactions (libido and ejaculation problems 5% and headache 5%) were mild and tolerant and did not require the interruption of the therapy. During a 24-week treatment of benign prostatic hyperplasia with tamsulosin, the same showed clinical efficiency in the sense of improvement of LUTS and a decrease of bladder outlet obstruction (BOO), without the influence on prostate volume or showing statistically significant vasodilatory effect. The same affected a significant decrease of ultrasound estimated bladder weight (from 65 g to 28 g).

Sedative, vasorelaxant, and cytotoxic effects of convolvulin from Ipomoea tyrianthina

Ipomoea tyrianthina has been used in Mexican traditional medicine as a mild purgative, for the treatment of nervous disorders, and against tumors. In this study, the effect of convolvulin (an ether-insoluble resin glycoside) from the root of Ipomoea tyrianthina on: Central Nervous System; as spasmolytic and vasodilator; cytotoxic against cancer cell lines is evaluated. Convolvulin isolated from the root of Ipomoea tyrianthina (IT-EM) was tested on pentylentetrazole induced seizures, pentobarbital-induced hypnosis, release of GABA and glutamic acid, isolated rat aorta and ileum rings, and against Caco-2 and KB cell lines. IT-EM increased the hypnotic effect induced by pentobarbital and the release of GABA in brain cortex of mice, but did not protect mice against pentylenetetrazole-induced convulsions. IT-EM produced a significant vasodilator effect in concentration- and endothelium-dependent manners on isolated rat aorta, but did not inhibit significantly contractions on rat ileum, colon, and jejune rings. IT-EM showed cytotoxic activity against nasopharyngeal carcinoma KB cell line. Convolvulin (IT-EM) from Ipomoea tyrianthina has sedative effect, vasorelaxant effect in concentration- and endothelium-dependent manners, and cytotoxic activity against nasopharyngeal carcinoma KB cell line.

Glyceryl trinitrate therapy for ischaemia, painful diabetic neuropathy, healing of foot ulceration and other podiatric conditions: a literature review

Glyceryl trinitrate is a substance that causes vasodilation by donation of nitric oxide which causes relaxation of the endothelium of blood vessel walls. The vasodilatory effect of this substance has been known since 1870 and it has been used extensively in the treatment of angina via transdermal patches, sublingual tablets and sprays. Studies involving normal vasculature as well as diseased vascular states have been promising in terms of demonstrably consistent and significant vasodilatory effects on both systemic and peripheral systems. Podiatric application for this pharmacologic intervention seems to have received little attention in the literature to date. Its efficacy in equine treatment of laminitis, an ischaemic condition of the horses hoof has been well established and researched. It has been applied to other clinical problems involving perfusion of the extremities, such as treatment of inability to achieve penile erection and use in treatment of anal fissures. A literature search has produced information on this drug which suggests potential for greater application in clinical podiatry. This includes positive effects in digital perfusion, which holds promise for wound healing and shows potential for reducing amputations associated with peripheral vascular disease (PVD). This novel therapy has the potential to be useful in cases with borderline vascular supply that require a boost to perfusion to trigger the healing process and/-or relieve other symptoms of ischaemia. It has also been found to be of assistance in the management of painful diabetic neuropathy (PND). This finding is of particular interest as an adjunct to treatment for the prevalent and difficult clinical challenge of PND. The literature regarding its use in musculotendinous applications such as for Achilles tendinopathy will also be covered in this review. Potential issues with this drug including side effects and tolerance will be addressed. Further study of this treatment modality would be beneficial in terms of determining specific indications and limitations of its use, particularly for vascular insufficiency of the feet and healing of foot ulceration.

Micropropagation and vasorelaxant activity of Laelia autumnalis (Orchidaceae)

A simple and efficient protocol has been developed in order to obtain healthy seedlings by asymbiotic germination of seeds from Laelia autumnalis. Seeds from mature capsules were germinated asymbiotically after being cultured on full- or half-strength Murashige and Skoog's (MS) medium, without plant growth regulators and with 3.0% or 1.5% of sucrose. The percentage of germinated seeds (% GS) was recorded during 6 weeks using three different conditions of incubation: light (80% GS, p < 0.05), darkness (30% GS) and white light photoperiod (100% GS, p < 0.05). The best seed germination percentages were found on the light and white light photoperiod conditions. Moreover, we also investigated the vasorelaxant action of the methanolic extracts from wild L. autumnalis (roots, pseudobulbs and leaves) and plantlets generated in vitro. Results showed that the methanolic extract of roots and pseudobulbs produced a significant vasodilator effect, in a concentration-dependent and endothelium-independent manner on norepinephrine (NE) and potassium chloride (KCl)-induced contractions in rat aortic thoracic rings. Nevertheless, the methanolic extract of leaves and plantlets showed no relevant vasorelaxant activity. Therefore, the results suggest that pseudobulbs and roots were the main tissues of the plant where vasorelaxant compounds are stored.

ORIGINAL RESEARCH—BASIC SCIENCE: Initial Characterization of Hydrogen Sulfide Effects in Female Sexual Function

ABSTRACT Introduction In our male animal models, hydrogen sulfide (H2S) displayed significant vasodilatory and smooth muscle relaxant effects suggestive of an endogenous physiological role in erectile process. Aim In this first exploratory study, we aimed to identify the existence and mechanism of H2S pathway in female sexual physiology. Methods Vaginal and clitoral cavernosal smooth muscle strips from New Zealand white rabbits (N = 12) were exposed to stable H2S donor, sodium hydrosulfide hydrate (NaHS.xH2O, 100 µM–1.6 mM), in isometric tension studies. The NaHS responses were repeated after incubations with (i) Nω-nitro-L-arginine (50 µM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 µM) or cis-N-[2-phenylcyclopentyl]-azacyclotridec-1-en-2-amine (MDL 12,330A) (10 µM); and (ii) potassium chloride medium (high K+ 60 mM/low K+ 10 mM), tetraethylammonium (10 mM) or glibenclamide (100 µM). Relaxant effect of NaHS was also compared with those of nitroglycerine (0.18–78.2 µM) and sildenafil (0.084–25.3 µM). Additionally, samples (N = 16) were collected for estimations of plasma and tissue H2S and expression levels of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) proteins. Main Outcome Measures In vitro evidences for H2S formation and its physiopharmacological effects. Results NaHS produced significant concentration-dependent relaxation of vaginal and cavernosal smooth muscles with inhibitions by combination of ODQ and MDL 12,330A (26.4%), Nω-nitro-L-arginine (22.2%), high K+ (15.1%) or glibenclamide (10.1%). Based on molar potency, NaHS was 18.3 and 6.3 times weaker than nitroglycerine and sildenafil, respectively. Quantitative assays indicated that plasma H2S level was 16.5 ± 2.58 µM, and H2S was synthesized in the clitoral and vaginal smooth muscles (1.8 and 3.9 nmol/mg soluble protein compared with 26.5 nmol/mg in the liver: positive control). Similarly, western blotting identified the protein expression bands of CSE (44.5 kDa) and CBS (63 kDa) in these genital tissue samples. Conclusion These pilot studies clearly indicate the smooth muscle relaxant effect of H2S in female genital tract, mediating through cyclic adenosine 3′:5′-monophosphate, nitric oxide-cyclic guanosine monophosphate and K+ATP channels. Taken together with biochemical and molecular evidences for endogenous formation, H2S pathway could be a contributing factor in female sexual responses.

Intracavernosal pressure responses to sodium nitrite

Till recently nitrite and nitrate were considered as inert biological end products of nitric oxide (NO) metabolism. However, studies in experimental animals and human subjects have shown that nitrite is reduced back to NO with significant vasodilator activity. The vadsoilatory effect of sodium nitrite in the corpus cavernosum (erectile function) has not yet been determined, and therefore was investigated. The erectile responses were evaluated by measuring intracavernosal pressure (ICP) with a 27 gauge needle placed in the crura. Intracavernosal (IC) injections of sodium nitrite (10 ‐ 100 µmol/kg) increased ICP in a dose‐dependent manner. The increases in pressure ranged from 5 to 50 mm Hg and were similar to responses elicited by IC injection of SNP. Maximum increases in ICP in response to sodium nitrite and SNP were similar to increases in pressure observed upon electrical stimulation of the corporal nerve. The IC injections of acetylcholine induced smaller increases in ICP than sodium nitrite or SNP. The IC injections of sodium nitrate however did not have any significant vasodilator effect. The results indicate that nitrite is converted to NO causing vasodilation and increases in cavernosal blood flow and erection in the rat. Additionally, it suggests that nitrite reductase activity is present in the corpora cavernousum of the rat and is consistent with the hypothesis that nitrite represents a storage form of NO.