Hypogastric Nerve Stimulation Research Articles

Feasibility and Efficacy of Transdermal Hypogastric Nerve Stimulation in Treatment of Overactive Bladder in Multiple Sclerosis: A Prospective Randomized Controlled Trial

Objective: To determine the feasibility and efficacy of transdermal hypogastric nerve stimulation by interferential current stimulation (IFCs) in the treatment of OABs in relapsing-remitting multiple sclerosis (RRMS). Material and Methods: Forty male RRMS patients with moderate overactive bladder symptoms were randomly assigned into two equal groups; the control group (G1) was treated with selected therapeutic exercises for strengthening the pelvic floor muscles, and the intervention group (G2) received the same regimen plus hypogastric nerve stimulation at T10-L2 by interferential current (IFC). In both groups, the duration of each session ranged from 40-45 minutes, three days weekly for a month. Pre and post treatment evaluation was done by Overactive bladder symptom score (OABSS) included (daytime frequency, nocturia, urgency, and urgency incontinence) and Urodynamics tests included (bladder capacity, maximum flow rate, bladder compliance, detrusor instability) and post voiding residual urine measurement by abdominal ultrasound. The effect of treatment on bladder capacity, maximum flow rate, post void residual, bladder compliance and OVBSS was investigated using a mixed MANOVA. The Mann Whitney test was used to evaluate the detrusor instability between groups, and the Wilcoxon signed ranks test was used to compare pre and post treatment in each group. The level of significance was set at p < 0.05 for all statistical tests. Results: Showed that a significant increase in bladder capacity, bladder compliance, percentage of detrusor stability and maximal flow rate and a significant decrease in post void residual post treatment in comparison with pretreatment (p < 0.05) in both groups. There was a significant decrease in the daytime and nighttime frequency and urgency post treatment compared with that pretreatment in both groups (p > 0.001) while a significant decrease of urgency incontinence in the study group only post treatment compared with that pretreatment (p > 0.001). Post treatment, there was a significant difference of the intervention group (G2) compared with that of the control group (G1) for all tested variables (P< 0.05) except for the daytime frequency and percentage of detrusor stability (p > 0.05). Conclusions: Transdermal hypogastric nerve stimulation using IFC could be considered a feasible treatment option for neurogenic OABs in multiple sclerosis patients.

Acute bladder decentralization in hound dogs: Preliminary results of effects on hypogastric nerve electroneurograms and detrusor pressure responses to spinal root and hypogastric nerve stimulation.

ObjectiveWe aimed to refine electroneurogram techniques for monitoring hypogastric nerve activity during bladder filling, and then examined nerve activity in normal intact versus acutely decentralized bladders.MethodsEffects of electrical stimulation of hypogastric nerves or lumbar ventral roots on detrusor pressure were examined, as were effects of isoflurane versus propofol anesthetics on hypogastric nerve stimulation evoked pressure. Hypogastric nerve activity was then recorded using custom-made bipolar cuff electrodes during bladder filling before and after its transection between the spinal cord and electrode to eliminate efferent nerve signals.ResultsElectrical stimulation of hypogastric nerves evoked low amplitude detrusor pressures that did not differ between the two anesthetics. Upper lumbar (L2) ventral root stimulation evoked detrusor pressures were suppressed, yet not eliminated, after transection of hypogastric nerves and all spinal roots below L5. Afferent and efferent hypogastric nerve activity did not change with bladder filling in neuronally intact bladders yet decreased in decentralized bladders. No change in afferent activity was observed during bladder filling in either intact or decentralized bladders.ConclusionsThese findings indicate that a more complete decentralized bladder model should include transection of lumbosacral spinal roots innervating the bladder as well as hypogastric nerves. These refined electroneurogram recording methods may be suitable for evaluating the effectiveness of nerve transfer surgeries for bladder reinnervation by monitoring sensory activity in the transferred nerve.

Comparison of the Effects of Tadalafil and α1-Adrenoceptor Antagonists on Spontaneous Seminal Emission and Electrical Field Stimulation-Induced Seminal Vesicle Contraction in Rats

BackgroundAlthough numerous reports have shown that α1-adrenoceptor (α1-AR) antagonists, which are used to treat benign prostatic hyperplasia (BPH), can cause ejaculatory disorders, few studies have investigated whether the phosphodiesterase 5 (PDE5) inhibitor tadalafil has such adverse effects. In this study, we compared the effects of tadalafil and α1-AR antagonists on seminal emission and their mechanisms of action. AimTo evaluate in normal rats the possible effects of tadalafil on spontaneous seminal emission (SSE) and seminal contraction evoked by hypogastric nerve stimulation. MethodsMale Sprague-Dawley rats were used. To assess SSE, plastic corsets were fitted around the thorax and upper abdomen of male Sprague–Dawley rats to prevent genital autogrooming. Rats were treated orally with tadalafil or an α1-AR antagonist (silodosin, naftopidil, or tamsulosin) for 3 days and housed in wire-bottomed cages. Ejaculatory plugs dropped on the bottoms of the cages were counted and weighed. To assess the intraluminal pressure of seminal vesicles, the hypogastric nerve of urethane-anesthetized rats was isolated and electrically stimulated. After stabilization of seminal vesicle contraction, the rats were intravenously administered test drugs. The expression of PDE5, endothelial nitric oxide synthetase (eNOS), and neuronal NOS (nNOS) in the seminal vesicle and vas deferens were measured by reverse-transcription polymerase chain reaction. Main Outcome MeasureThe number and weight of the ejaculatory plugs produced by corset-fitted rats and the intraluminal pressure of the seminal vesicle were evaluated. ResultsTadalafil did not affect the number or weight of the ejaculatory plugs of corset-fitted rats, whereas all α1-AR antagonists decreased both in a dose-dependent manner. The α1-AR antagonists, but not tadalafil, inhibited the seminal vesicle contraction evoked by electrical stimulation of the hypogastric nerve. The seminal vesicle and vas deferens expressed higher levels of PDE5 and eNOS mRNA and lower levels of nNOS mRNA relative to the urethra. Clinical ImplicationsTadalafil can be a treatment option in cases where there is concern about negative effects on seminal emission. Strengths and LimitationsWe demonstrated different effects of tadalafil and 3 α1-AR antagonists on rat SSE and their mechanisms of action by measuring seminal vesicle contractility in vivo. A limitation is that we used normal rats, not BPH model rats, and so our results might not apply to human BPH patients. ConclusionTadalafil did not inhibit spontaneous seminal emission or electrical field stimulation–induced seminal vesicle contraction in normal rats. The NO–cyclic guanosine monophosphate pathway is unlikely to be involved in the inhibition of seminal vesicle contraction in normal rats.Yoshinaga R, Fukui T, Yoshifuji M, et al. Comparison of the Effects of Tadalafil and α1-Adrenoceptor Antagonists on Spontaneous Seminal Emission and Electrical Field Stimulation-Induced Seminal Vesicle Contraction in Rats. J Sex Med 2019;16:680–690.

Sympathetic afferents in the hypogastric nerve facilitate nociceptive bladder activity in cats.

This study in α-chloralose-anesthetized cats revealed a role of hypogastric nerve afferent axons in nociceptive bladder activity induced by bladder irritation using 0.25% acetic acid (AA). In cats with intact hypogastric and pelvic nerves, AA irritation significantly ( P < 0.05) reduced bladder capacity to 45.0 ± 5.7% of the control capacity measured during a saline cystometrogram (CMG). In cats with the hypogastric nerves transected bilaterally, AA irritation also significantly ( P < 0.05) reduced bladder capacity, but the change was significantly smaller (capacity reduced to 71.5 ± 10.6% of saline control, P < 0.05) than that in cats with an intact hypogastric nerve. However, application of hypogastric nerve stimulation (HGNS: 20 Hz, 0.2 ms pulse width) to the central end of the transected nerves at an intensity (16 V) strong enough to activate C-fiber afferent axons facilitated the effect of AA irritation and further ( P < 0.05) reduced bladder capacity to 48.4 ± 7.4% of the saline control. This facilitation by HGNS was effective only at selected frequencies (1, 20, and 30 Hz) when the stimulation intensity was above the threshold for activating C-fibers. Tramadol (an analgesic agent) at 3 mg/kg iv completely blocked the nociceptive bladder activity and eliminated the facilitation by HGNS. HGNS did not alter non-nociceptive bladder activity induced by saline distention of the bladder. These results indicate that sympathetic afferents in the hypogastric nerve play an important role in the facilitation of the nociceptive bladder activity induced by bladder irritation that activates the silent C-fibers in the pelvic nerve.

AB319. SPR-46 In vivo hypogastric nerve electrical stimulation contracts the canine detrusor

ObjectiveOur goal was to determine whether electrical stimulation of the hypogastric nerve in dogs with intact bladder innervation results in contraction of the detrusor muscle of the bladder. The effects of the anesthetics isoflurane versus propofol on detrusor pressure with hypogastric nerve stimulation were compared.MethodsA total of 14 female mixed-breed hounds with intact bladder innervation, body mass of 20–25 kg and 6–8 months of age were used. Maximum changes in detrusor pressures were determined following electrical stimulation (3–10 mA, 20 Hz) of the hypogastric nerves under isoflurane inhalation anesthesia at 1–3% mean alveolar concentration in oxygen (n=14). Five of these same dogs were then transitioned to propofol anesthesia administered intravenously by continuous-rate infusion (0.3–0.5 mg/kg/min). Detrusor pressures were recorded at a sampling rate of 4/s using PowerLab software (AD Instruments) and displayed using LabChart. Following electrical stimulation, hypogastric nerves were harvested from five dogs undergoing decentralization for other experiments. These nerves were cryosectioned and examined for expression of the adrenergic marker enzyme tyrosine hydroxylase (present in sympathetic peripheral nerves) using immunohistochemical methods.ResultsElectrical stimulation of the hypogastric nerve caused an increase in detrusor pressure (2 to 9 cmH2O) under isoflurane anesthesia in 11 of 14 dogs. Two of the 5 dogs tested under propofol anesthesia showed an increase in detrusor pressure after switching from isoflurane to propofol, another showed no change, and the remaining two showed an absence of bladder contractions in response to hypogastric nerve stimulation under either anesthetic. Each collected hypogastric nerve showed positive tyrosine hydroxylase immunostaining, confirming that the nerves contain sympathetic fibers.ConclusionsThese results indicate that the neuronally intact canine detrusor muscle contracts during hypogastric nerve stimulation under both isoflurane and propofol anesthesia. These results confirm findings by de Groat and colleagues in cats and by Elmer in rats showing that electrical stimulation of hypogastric nerves in animals with intact bladder innervation elicits low-amplitude bladder contractions.Funding Source(s)NIH-NINDS NS070267

A Nonhuman Primate Model of Stable Urinary Sphincter Deficiency

The pathophysiology of urinary sphincter deficiency in women remains incompletely understood and current treatment options have limitations. Female nonhuman primates may represent a relevant animal model for studies of pathophysiology and treatment interventions because of their human-like reproductive and age associated stages of life (premenopause, perimenopause and postmenopause), lower urinary tract structure and bipedal posture. We developed and characterized a nonhuman primate model of defined injury to the urethral sphincter complex. We used 22 adult female cynomolgus monkeys in which injury to the sphincter complex was created by cauterizing and then transecting its pudendal innervation. Urodynamic studies were performed before and during pudendal and hypogastric nerve stimulation at baseline, and 3, 6 and 12 months after injury. We also analyzed sphincter structure in vivo by cystourethrography, and ex vivo by quantitative histology and immunohistochemistry at these time points. Injury produced a 47% to 50% decrease in maximal urethral pressure (vs baseline p <0.05). It also abolished the increase in maximal urethral pressure in response to pudendal and hypogastric nerve stimulation (vs baseline p >0.05), which persisted more than 12 months after injury. Urodynamic changes were consistent with decreased skeletal and smooth muscle content, decreased nerve responses and an associated decrease in somatic and adrenergic innervation in the sphincter complex. These structural and urodynamic changes are consistent with those in patients with stress urinary incontinence. They support the usefulness of nonhuman primates as translatable surrogates for pathophysiological studies of urinary sphincter deficiency and testing novel therapies for that condition.

9‐Hydroxycanthin‐6‐One Induces Penile Erection and Delays Ejaculation

Eurycoma longifolia Jack (Simaroubaceae) has the reputation as a male aphrodisiac because it is claimed to increase virility and sexual prowess. Nevertheless, whether or not E. longifolia regulates directly the muscle tone of corpus cavernosa and/or seminal vesicle (SV) remains unclear. Even until now, the compositions that could account for its aphrodisiac property are still unknown We examined the effect of 9-hydroxycanthin-6-one (9-HC-6-one), a β-carboline alkaloid isolated from E. longifolia, on penile erection and ejaculation, and further elucidated the mechanism of action. 9-HC-6-one induces penile erection and delays ejaculation. Drug's effect was studied on rat corpus cavernosum (CC) and SV in vitro, and on the changes in intracavernosal pressure (ICP) after IC injection and intraluminal pressure (ILP) of the SV after hypogastric nerve stimulation (HNS), respectively. 9-HC-6-one relaxed significantly phenylephrine (PE)-precontracted CC. Such response was not attenuated by endothelium disruption, N(G) -nitro-L-arginine methyl ester, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one treatment, suggesting that a nitric oxide/cyclic guanosine monophosphate-dependent pathway was precluded. 9-HC-6-one attenuated PE-induced contraction by blocking cell surface and internal calcium channels with a higher potency for internal calcium release. This compound also antagonized calcium-evoked contraction in Ca2+ -free, high K+ -depolarizing condition, suggesting that interfering with the entry of calcium through voltage-dependent channels also contributed to 9-HC-6-one-induced corporal relaxation. After IC application of 9-HC-6-one, a significant rise in ICP was observed as compared with the application of normal saline. 9-HC-6-one relaxed significantly norepinephrine (NE)- and KCl-precontracted SV, and antagonized NE-induced oscillatory contraction as potent as clomipramine. Finally, the HNS-evoked increase in ILP was dose-dependently repressed after challenge by 9-HC-6-one. 9-HC-6-one might be the active component that contributed to the aphrodisiac effect of E. longifolia by antagonizing the smooth muscle tone of CC as well as SV probably through interfering with Ca2+ mobilization.

Some effects of pilocarpine and acetylcholine on the responses of the guinea-pig vas deferens to hypogastric nerve stimulation and transmural stimulation and applied (–)-noradrenaline

Enhancement by acetylcholine and by pilocarpine of the contractile responses of the guinea-pig isolated vas deferens to hypogastric nerve and transmural stimulation and to exogenous (minus)-noradrenaline was examined. At high concentration (600 nM) acetylcholine enhanced responses in the order:hypogastric nerve greater than transmural greater than exogenous (minus)-noradrenaline. Pilocarpine produced a similar maximal degree of enchancement with all three stimuli. All these effects were reversibly inhibited by 1-4 mum atropine, a concentration which alone did not affected responses to the stimuli. Pilocarpine (50-400 muM) gave a concentration-related inhibition of the enhancement of responses to hypogastric nerve stimulation by 600 nM acetylcholine.

Effects of autonomic nerve stimulation on colorectal motility in rats

Several disease processes of the colon and rectum, including constipation and incontinence, have been associated with abnormalities of the autonomic nervous system. However, the autonomic innervation to the colon and rectum are not fully understood. The aims of this study were to investigate the effect of stimulation of vagus nerves, pelvic nerves (PN) and hypogastric nerves (HGN) on colorectal motility in rats. Four strain gauge transducers were implanted on the proximal colon, mid colon, distal colon and rectum to record circular muscle contractions in rats. Electrical stimulation was administered to the efferent distal ends of the cervical vagus nerve, PN and HGN. Motility index (MI) was evaluated before and during stimulation. Electrical stimulation (5-20 Hz) of the cervical vagus elicited significant contractions in the mid colon and distal colon, whereas less pronounced contractions were observed in the proximal colon. Pelvic nerves stimulation elicited significant contractions in the rectum as well as the mid colon and distal colon. Atropine treatment almost completely abolished the contractions induced by vagus nerve and PN stimulation. Hypogastric nerves stimulation caused relaxations in the rectum, mid colon and distal colon. The relaxations in response to HGN stimulation were abolished by propranolol. Vagal innervation extends to the distal colon, while the PN has projections in the distribution of the rectum through the mid colon. This suggests a pattern of dual parasympathetic innervation in the left colon. Parasympathetic fibers regulate colorectal contractions via muscarinic receptors. The HGN mainly regulates colorectal relaxations via beta-adrenoceptors.

Sympathetic and Parasympathetic Regulation of Rectal Motility in Rats

IntroductionThe colon and rectum are regulated by the autonomic nervous system (ANS). Abnormalities of the ANS are associated with diseases of the colon and rectum while its modulation is a putative mechanism for sacral nerve stimulation. The purpose of this study is to establish a rat model elucidating the role of the efferent ANS on rectal motility. Materials and MethodsRectal motility following transection or stimulation of parasympathetic pelvic nerves (PN) or sympathetic hypogastric nerves (HGN) was measured with rectal strain gauge transducers and quantified as a motility index (MI). Colonic transit was measured 24 hours after transection by calculating the geometric center (GC) of distribution of 51Cr Results and DiscussionTransection of PN and HGN decreased MI to 518 ± 185 g•s (p < 0.05) and increased MI to 5,029 ± 1,954 g•s (p < 0.05), respectively, compared to sham (975 ± 243 g•s). Sectioning of PN and HGN decreased transit with GC = 4.9±0.2 (p < 0.05) and increased transit with GC = 8.1±0.7 (p < 0.02), respectively, compared to sham (GC = 5.8 ± 0.3). Stimulation of PN and HGN increased MI to 831 ± 157% (p < 0.01) and decreased MI to 251 ± 24% (p < 0.05), respectively. ConclusionRectal motility is significantly altered by sectioning or stimulating either HGN or PN. This model may be useful in studying how sacral nerve stimulation exerts its effects and provide insight into the maladies of colonic motility.

Changes of ejaculation due to suppression of noradrenaline biosynthesis by diethyldithiocarbamate in dogs: a supplemental report with reference to changes of posterior urethral pressure.

In the preceding paper (Kimura et al.-1979) it was reported that diethyldithiocarbamate suppresses ejaculation, although penile erection is maintained, and that the suppression is not mediated by the central nervous system but by the decrease of catecholamine contents in the organs relating to sperm transport. In this paper, changes of ejaculation following administration of diethyldithiocarbamate was studied with the posterior urethrogram; measurement of the posterior urethral pressure during hypogastric nerve stimulation. From the results obtained in this study the above results were confirmed. It was also confirmed that both seminal emission and ejaculation are under the influence of an alpha-adrenergic receptor mechanism. Also, a dopamine receptor mechanism was suspected to be present in the male accessory sexual glands.

Effects of silodosin and tamsulosin on the urethra and cardiovascular system in young and old dogs with benign prostatic hyperplasia

We examined whether the effects (efficacy on the urethra and hypotension) of silodosin (α 1A-adrenoceptor antagonist) and tamsulosin (α 1A + 1D -adrenoceptor antagonist) in dogs with benign prostatic hyperplasia altered with age. We used young and old dogs, diagnosed as having benign prostatic hyperplasia by veterinarian's palpation. Under anesthesia, the increase in intraurethral pressure evoked by hypogastric nerve stimulation was measured, together with the level of systemic mean blood pressure. Each drug was administered intravenously in progressively increasing doses. At the end of the experiment, the prostate was isolated from each dog, then weighed and investigated pathologically to confirm benign prostatic hyperplasia. The wet weight of the prostate was greater in old dogs with benign prostatic hyperplasia than in young dogs with benign prostatic hyperplasia. By light microscopy, hyperplasia in the prostatic epithelium was confirmed in both groups. Silodosin (0.3–300 μg/kg) dose-dependently inhibited the hypogastric nerve stimulation-induced increase in intraurethral pressure (without significant hypotensive effects) in both young and old dogs with benign prostatic hyperplasia. Tamsulosin (0.3–300 μg/kg) also dose-dependently inhibited the intraurethral pressure increase in both groups, but it had a hypotensive effect that was significantly greater in old than in young dogs with benign prostatic hyperplasia. In conclusion, as regards the effect of silodosin on intraurethral pressure, potency was similar between young and old dogs with benign prostatic hyperplasia, and it was without significant hypotensive effects. We therefore suggest that silodosin might be a good medication for lower urinary tract symptoms in patients with benign prostatic hyperplasia in all age groups.

Effect of Silodosin on Intraurethral Pressure Increase Induced by Hypogastric Nerve Stimulation in Dogs with Benign Prostatic Hyperplasia

Effect of Silodosin on Intraurethral Pressure Increase Induced by Hypogastric Nerve Stimulation in Dogs with Benign Prostatic Hyperplasia

Ano‐rectal motility responses to pelvic, hypogastric and pudendal nerve stimulation in the Göttingen minipig

We investigated the effect of efferent stimulation of the pelvic (PN), hypogastric (HGN) and pudendal (PuN) nerves on ano-rectal motility in Göttingen minipigs using an impedance planimetry probe. Changes in the rectal cross-sectional area (CSA) at five axial positions and pressures in the rectum and anal canal were investigated simultaneously. Pelvic nerve stimulation elicited a CSA decrease in the proximal part of the rectum and a simultaneous CSA increase in its distal part. Anal pressure also decreased. Hypogastric nerve and PuN stimulation elicited an increase in anal pressure, but no rectal response. Severing the HGN produced a persistent reduction in resting anal pressure, but no change was observed when the PN and the PuN were severed. Stimulation of the distal part of all three nerves produced a persistent response. Administration of phentolamine and pancouronium eliminated the response to stimulation of the HGN and the PuN, respectively. Rectal responses to PN stimulation vary more than previously suggested. The HGN has an excitatory effect on the internal anal sphincter, and the PuN on the external anal sphincter. However, the PuN plays no major role in maintaining basal anal pressure.

Uroselectivity in male dogs of silodosin (KMD‐3213), a novel drug for the obstructive component of benign prostatic hyperplasia

Our main aim was to compare the prostatic selectivity of silodosin with that of other alpha(1)-adrenoceptor (AR) antagonists. We examined uroselectivities in two sets of experiments namely, in vitro and in vivo functional studies using male dogs. In the in vitro study, after evaluating the inhibitory effects of silodosin on noradrenaline (NA)-induced contractions in the isolated prostate and isolated carotid artery using the Magnus method, we calculated prostatic selectivity. In the in vivo study, we examined the effects of drugs on the hypogastric nerve stimulation (HNS)-induced increase in intraurethral pressure (IUP) and on blood pressure. The uroselectivity of silodosin was compared with those of tamsulosin and naftopidil. In vitro, all drugs antagonized NA-induced contraction in both prostate and carotid artery. The prostatic selectivity of silodosin (79.4) was much higher than those of tamsulosin (1.78), naftopidil (0.55), BMY 7378 (0.115), and prazosin (0.01). In vivo, intravenously (i.v.) administered silodosin dose-dependently inhibited the HNS-induced increase in IUP with much less hypotensive effect than either tamsulosin or naftopidil, the uroselectivity (ED(15)/ID(50)) of silodosin (237) being significantly higher than those of tamsulosin (1.21) and naftopidil (2.65). Our results clearly demonstrate that silodosin is a potent and highly selective alpha(1A)-AR antagonist. A selective alpha(1A)-AR antagonist such as silodosin may have good potential as a less-hypotensive drug for the treatment of urinary dysfunction in benign prostatic hyperplasia patients.

Effect of Silodosin on Intraurethral Pressure Increase Induced by Hypogastric Nerve Stimulation in Dogs with Benign Prostatic Hyperplasia

We compared the urethral and cardiovascular effects of silodosin (selective alpha(1A)-adrenoceptor antagonist), a novel medication for benign prostatic hyperplasia (BPH), with those of tamsulosin (selective alpha(1A)/alpha(1D)-adrenoceptor antagonist) and naftopidil (selective alpha(1D)-adrenoceptor antagonist). We evaluated the effects of these three drugs on the increase in intraurethral pressure (IUP) induced by electrical stimulation of the hypogastric nerve in anesthetized dogs with spontaneous BPH. All three drugs dose-dependently reduced both the increase in IUP and the mean blood pressure (MBP). The rank order of potencies was tamsulosin>silodosin>naftopidil for the reductions in both IUP and MBP. However, the uroselectivity (ED(15) value for hypotensive effect/ID(50) value for reduction in IUP) of silodosin (uroselectivity, 19.8) was about 21 and 4 times higher than that of tamsulosin (0.939) and naftopidil (4.94), respectively. These data suggest that silodosin might be one of the most useful medications for dysuria in BPH patients.

Peripheral effects of serotonin on the contractile responses of rat seminal vesicles and vasa deferentia.

With the central effects of serotonin (5-HT) on ejaculation having been relatively established, we investigated the peripheral effects of serotonin on the contractile responses of rat seminal vesicles and vasa deferentia. Male Sprague-Dawley rats were grouped on the basis of the agents administered: serotonin, clomipramine, or fluoxetine. The intraluminal pressures of the seminal vesicles and of the vasa deferentia were measured simultaneously. Control responses to hypogastric nerve stimulation (HNS) were recorded in each animal, and HNS was repeated after drug administration. Expression of the mRNAs of the 5-hydroxytryptamine (5-HT) receptors (5-HT1A, 5-HT1B, and 5-HT2C), which have been suggested to be involved in the ejaculation process, were examined by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Serotonergic agents resulted in the concentration-dependent inhibition of HNS-induced seminal vesicle pressure increases (clomipramine > serotonin > fluoxetine). Vasal pressure responses were effectively inhibited by clomipramine and serotonin, but fluoxetine had no effect. No significant difference was observed in the relative expression levels of 5-HT1A receptor mRNA in seminal vesicles and in the vasa deferentia. However, the expression levels of 5-HT1B and 5-HT2C receptor mRNAs were lower in the vasa deferentia than in the seminal vesicles. These in vivo and in vitro experimental results provide evidence for the peripheral role of 5-HT in the regulation of contractile responses of the seminal tract. Regional differences in the distribution of the 5-HT receptor subtypes of the seminal vesicles and the vasa deferentia might contribute to the different responses to serotonergic agents shown by these organs.

In vivo rat model to measure hypogastric nerve stimulation-induced seminal vesicle and vasal pressure responses simultaneously.

This study presents a modified in vivo model in which the intraluminal pressures of the seminal vesicle and vas deferens can be measured simultaneously. Male Sprague-Dawley rats were grouped based on agent administered: serotonin, clomipramine, fluoxetine, sertraline, paroxetine, prazosin, terazosin, and tamsulosin. The control responses to hypogastric nerve stimulation (HNS) were recorded in each animal, and HNS was repeated after each drug administration. Serotonergic agents resulted in concentration-dependent inhibition of the HNS-induced seminal vesicle pressure increases (clomipramine>serotonin>fluoxetine>sertraline approximately paroxetine). On the other hand, only serotonin and clomipramine significantly inhibited vasal pressure responses. alpha-Adrenergic blockers inhibited both intraluminal pressure responses in a concentration-dependent manner. This model illustrates the importance of the hypogastric nerve for the stimulation of the seminal tract, with attention focused on the seminal vesicle. This model may be useful for the evaluation of drugs for the treatment of premature ejaculation.

Differential expression of calcium channels in sympathetic and parasympathetic preganglionic inputs to neurons in paracervical ganglia of guinea-pigs

Neurons in pelvic ganglia receive nicotinic excitatory post-synaptic potentials (EPSPs) from sacral preganglionic neurons via the pelvic nerve, lumbar preganglionic neurons via the hypogastric nerve or both. We tested the effect of a range of calcium channel antagonists on EPSPs evoked in paracervical ganglia of female guinea-pigs after pelvic or hypogastric nerve stimulation. ω-Conotoxin GVIA (CTX GVIA, 100 nM) or the novel N-type calcium channel antagonist, CTX CVID (100 nM) reduced the amplitude of EPSPs evoked after pelvic nerve stimulation by 50–75% but had no effect on EPSPs evoked by hypogastric nerve stimulation. Combined addition of CTX GVIA and CTX CVID was no more effective than either antagonist alone. EPSPs evoked by stimulating either nerve trunk were not inhibited by the P/Q calcium channel antagonist, ω-agatoxin IVA (100 nM), nor the L-type calcium channel antagonist, nifedipine (30 μM). SNX 482 (300 nM), an antagonist at some R-type calcium channels, inhibited EPSPs after hypogastric nerve stimulation by 20% but had little effect on EPSPs after pelvic nerve stimulation. Amiloride (100 μM) inhibited EPSPs after stimulation of either trunk by 40%, while nickel (100 μM) was ineffective. CTX GVIA or CTX CVID (100 nM) also slowed the rate of action potential repolarization and reduced afterhyperpolarization amplitude in paracervical neurons. Thus, release of transmitter from the terminals of sacral preganglionic neurons is largely dependent on calcium influx through N-type calcium channels, although an unknown calcium channel which is resistant to selective antagonists also contributes to release. Release of transmitter from lumbar preganglionic neurons does not require calcium entry through either conventional N-type calcium channels or the variant CTX CVID-sensitive N-type calcium channel and seems to be mediated largely by a novel calcium channel.

Differential effect of electrical stimulation of spinal and hypogastric nerves on parameters characterizing ejaculation in anaesthetized rats

Differential effect of electrical stimulation of spinal and hypogastric nerves on parameters characterizing ejaculation in anaesthetized rats