Influence of renal nerves on renal function during development

The present review summarizes recent studies describing the role of renal sympathetic innervation in the regulation of renal function during development. The afferent renal innervation appears early during fetal life and probably precedes the development of efferent renal nerves. There is suggestive evidence that renal nerves are required for the proper development of the kidney and that neurotrophic growth factors play an important role in renal embryogenesis and in renal tubular differentiation. Renal sympathetic innervation modulates renal hemodynamics early during development. Renal nerve stimulation during -adrenoceptor blockade produces renal vasodilation in fetal and newborn animals but not in adults. Unlike the effect of renal nerves on fetal renal hemodynamics which is observed in the young fetus, the role of renal sympathetic nerves in modulating fluid and electrolyte homeostasis seems to develop during late gestation. Recent studies have also shown that renal nerves play an important role in regulating renin secretion during the transition from fetal to newborn life. For example, renal denervation during fetal life suppressed the physiological rise in plasma renin activity associated with delivery and decreased renal renin mRNA levels after birth. Taken together, these studies suggest that renal nerves influence fetal renal development and that the influence of renal sympathetic innervation on renal hemodynamics and function changes with maturation.     

The renal nerves in the newborn rat

Immunocytochemical methods were used to investigate the distribution of afferent [calcitonin gene-related peptide-(CGRP) immunoreactive and substance P-immunoreactive] nerves and efferent (neuropeptide Y-immunoreactive and dopamine -hydroxylase-immunoreactive) nerves in the kidneys of rats within the 1st day of life. The newborn rat kidney possesses an afferent and efferent innervation. Both afferent and efferent nerves reach the kidney in the same bundles. The afferent sensory fibers predominate overwhelmingly in the renal pelvis and ureter while the efferent fibers clearly predominate in the vasculature. The corticomedullary connective tissue contains both types of innervation with a more prominent afferent innervation (CGRP immunoreactive). Only afferent arterioles of perihilar nephrons were innervated by efferent sympathetic fibers. The distribution and extent of afferent and efferent innervation is consistent with the renal nerves playing a significant role in the transition from fetal to newborn life. The close proximity between afferent and efferent fibers suggests a possible interaction between the two systems.     

Regulation of the bladder neck closure by lumbar splanchnic nerves at ejaculation in the dog

To clarify the role of canine thoracolumbar splanchnic nerves for bladder neck closure during ejaculation, these nerves of adult male mongrel dogs were exposed under anesthesia using ketamine hydrochloride and pentobarbital, and electrical stimulation and anatomical dissection studies were performed. Bladder neck closure by the stimulation of each sympathetic nerve was monitored with a 10 Fr silicon catheter equipped with pressure-sensitive rubber balloon placed at the bladder neck. The dissection study revealed that canine thoracolumbar splanchnic nerves consisted of two nerve groups: one branching from the sympathetic trunks at thoracic and L1 ganglia, reaching caudal mesenteric plexus (CMP) through the anterior wall of the aorta, the other branching from the sympathetic trunks at level L2–L5 ganglia, reaching CMP through the posterior side of the bilateral spermatic arteries. The former were designated intermesenteric splanchnic nerves, the latter lumbar splanchnic nerves. No bladder neck closure was observed by electrical stimulation of the distal end of severed intermesenteric splanchnic nerves or of the sympathetic trunks at the lumbopelvic level among 10 dogs examined. At least one lumbar splanchnic nerve generated the closure in all 10 dogs and generally, a few lumbar splanchnic nerves, generated the closure. The results indicate that bladder neck closure during ejaculation is generated by lumbar splanchnic nerves regardless of their branching levels from lumbar sympathetic ganglia, but not by either intermesenteric splanchnic nerves or pelvic sympathetic trunks. © 1993 Wiley-Liss, Inc.     

Effects of sevoflurane on autonomic nerve activities controlling cardiovascular functions in rats

Effects of different inspiratory concentrations of sevoflurane (fluorometyl-1,1,1,3,3,3,-hexafluoro-2-propylether) on blood pressure, heart rate and efferent activities of cardiac sympathetic, cardiac parasympathetic and renal sympathetic nerves were examined using rats either under the resting condition or during noxious mechanical stimulation of a hindpaw. Under the resting condition, an increase in the inspiratory concentration of sevoflurane from 2.1% to 4.2% gradually caused a decrease in blood pressure and heart rate. With the increase in the sevoflurane concentration, cardiac sympathetic nerve activity decreased, whereas renal sympathetic nerve and cardiac parasympathetic nerve activities did not change significantly. When noxious mechanical stimulation was applied to a hind-paw by pinching, blood pressure and heart rate, renal sympathetic and cardiac sympathetic nerve activities all increased at the 2.1% concentration of sevoflurane. The responses of these parameters were attenuated at the 3.1% concentration of sevoflurane and almost disappeared at the 4.2% concentration. Cardiac parasympathetic nerve activity did not change significantly during the pinching stimulation throughout the 2.1–4.2% concentration increase.(Kurosawa M, Meguro K, Nagayama T et al.: Effects of sevoflurane on autonomic nerve activities controlling cardiovascular functions in rats. J Anesth 3: 109–117, 1989)     

经皮射频导管消融肾脏去交感神经支配术治疗顽固性高血压

目的总结经皮射频导管消融肾脏去交感神经支配治疗顽固性高血压的效果和前景。方法通过文献检索,总结肾脏交感神经与高血压的关系,经皮射频导管消融肾脏去交感神经支配术在治疗顽固性高血压中的应用,以及此项技术的前景和不足。结果高血压作为一个严重的公共卫生问题,是目前临床治疗的重点。肾脏交感神经在血压调控的各方面都扮演着重要的角色,经皮射频导管消融肾脏去交感神经支配术在治疗顽固性高血压方面展示了极大的优越性。结论经皮射频导管消融肾脏去交感神经支配术在治疗顽固性高血压方面有着潜在的临床应用价值。     

Neurophysiological aspects of penile erection: the role of the sympathetic nervous system

Recent studies have revealed that the initiation, maintenance and rigidity of penile erection are under parasympathetic and somatotopic control. The mechanism of penile detumescence is still under debate. Single and combined cavernous and hypogastric nerve stimulation was used to study the influence of the sympathetic nervous system on penile erection and to identify the mechanism of penile detumescence. Penile arterial flow and intracorporeal pressure recordings during various stimulation patterns indicated that erection induced by stimulation of the cavernous nerve could be blocked by excitation of the upper hypogastric nerves. Venous outflow studies demonstrated that the inhibitory effect of the sympathetic nervous system was due to active vaso- and corporeal smooth muscle constriction. It was concluded that subsidence and suppression of erection is a sympathetic function. Previous studies have shown that the neurophysiology of erection can be explained by 3 major inhibitory (sympathetic). Our findings are of clinical importance, since a better appreciation of the basic erectile mechanism is essential for successful management of erectile dysfunction.     

Sympathetic overactivity--the Cinderella of cardiovascular risk factors in dialysis patients

Cardiovascular morbidity and mortality is exceedingly high in patients with chronic renal failure. Sympathetic overactivity is an important pathomechanism contributing to progression of renal disease as well as cardiovascular complications. For more than 30 years it has been known that plasma levels of norepinephrine are elevated in chronic renal failure pointing to increased sympathetic nerve activity. The kidneys are richly innervated by efferent sympathetic and afferent sensory nerves. They participate in many reflex adjustments of renal function. Initially, this finding had not been attributed to increased efferent sympathetic drive, but rather to reduced renal clearance and defective neuronal reuptake of norepinephrine.
At this time, however, the evidence for increased sympathetic drive is solid. Interventions to reduce sympathetic overactivity will provide new therapeutic approaches. The available experimental and clinical evidence to suggest such a pathophysiological role of sympathetic overactivity is summarized in this current review.     

The sympathetic nervous system in clinical and experimental hypertension

In summary, many lines of evidence indicate that the sympathetic nervous system, via the renal nerves, plays an important role in the pathogenesis of renovascular hypertension in humans and laboratory animals. Patients with established renovascular hypertension have increased sympathetic nervous system activity, as evidenced by increased plasma and urinary norepinephrine levels, elevated excretion of catecholamine metabolites, and an exaggerated depressor response to centrally acting sympatholytic agents. The observation that converting enzyme inhibitors can cause both blood pressure and urinary norepinephrine excretion to return to normal in patients with renovascular hypertension is consistent with the interpretation that activation of the sympathetic nervous system in these subjects is, at least in part, angiotensin-induced. The sympathetic nervous system, via the efferent renal nerves, plays a role in the pathogenesis of hypertension in a number of experimental models. In the spontaneously hypertensive rat of the Okamoto strain (SHR) and in the DOCA/NaCl hypertensive model, increased renal efferent nerve activity contributes to the development of hypertension by causing increased renal sodium retention. In both of these experimental models, renal denervation delays the development and blunts the severity of hypertension. This delay is associated with increased urinary sodium excretion, suggesting a renal efferent mechanism. In contrast to the predominantly efferent renal nerve mechanisms observed in the DOCA-NaCl and SHR models, studies of the effects of renal denervation in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats suggest that renal afferent nerves are important in these models of hypertension. Total renal denervation in rats with established 1K, 1C and 2K, 1C hypertension attenuates the severity of the hypertension without altering sodium intake or excretion, renin activity, water intake, or renal function. Thus, efferent renal nerve activity does not appear to be involved in the development of maintenance of 1K, 1C or 2K, 1C hypertension. In contrast with the findings in SHR and DOCA-NaCl rats, these studies provide indirect evidence that the renal afferent nerves play a role in the pathogenesis of this form of experimental hypertension. The major effect of renal denervation in these models appears to be an interruption of renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure.(ABSTRACT TRUNCATED AT 400 WORDS)     

Assessment of the method and timing of repair of a brachial plexus traction injury in an animal model for obstetric brachial plexus palsy

A Sunderland type IV traction injury to the C6 root of adult sheep or newborn lamb brachial plexus was used as a model for obstetric traction injury to the C5 root in humans. In one experimental cohort the injury was created and repaired using interfascicular nerve autografts or coaxially aligned freeze-thawed skeletal muscle autografts in a group of adult sheep and in a group of newborn lambs. In a second cohort a similar injury was created and repaired either immediately or after a delay of 30 days, using either interfascicular nerve autografts or coaxially aligned freeze-thawed skeletal muscle autografts in four groups of six newborn lambs. In all cases both functional and morphometric indices of nerve regeneration were poorer in the injured and repaired nerves than in normal nerves. In lambs the method of repair made no difference and no significant differences were found for any of the indices of nerve function or morphology. In sheep the use of muscle grafts was associated with a poorer outcome than the use of nerve autografts. Where a delay of 30 days had elapsed between injury and repair, the results using nerve autografts were not significantly different. Where freeze-thawed muscle autografts had been used, the maturation of the regenerated nerve fibres after delay was significantly poorer than after immediate repair. The electrophysiological variables CV(max) and jitter, which may be applied clinically, were found to be good discriminators of recovery in all of the animals and in respect of all procedures.     

Ipsilateral seminal emission generated by electrostimulation of the lumbar sympathetic nerve during nerve sparing laparoscopic retroperitoneal lymph node dissection for testicular cancer

PURPOSE: To confirm nerve preservation during laparoscopic retroperitoneal lymph node dissection we perform electrostimulation of the lumbar sympathetic nerves relevant to ejaculation. In recent cases we monitored seminal emission using endoscopy of the posterior urethra to observe the response to stimulation. MATERIALS AND METHODS: Six patients with testicular tumors underwent intraoperative stimulation of the lumbar sympathetic nerves during laparoscopic retroperitoneal lymph node dissection with a unilateral modified template. A long handled pair of bipolar electrodes was inserted through a laparoscopic port, and ipsilateral and contralateral lumbar sympathetic nerves were individually electrostimulated. Ipsilateral stimulation was performed at the preserved lumbar splanchnic nerves and contralateral stimulation was performed at the union of nerve fibers derived from the lumbar splanchnic nerve just above the superior hypogastric plexus. The side of generated seminal emission was monitored simultaneously by endoscopy of the posterior urethra. RESULTS: In all patients each electrostimulation generated unilateral seminal emission. Each stimulation of a lumbar splanchnic nerve, whether ipsilateral or contralateral, caused seminal emission only from the ejaculatory orifice of the stimulated side. CONCLUSIONS: Intraoperative electrostimulation of the lumbar sympathetic nerves generated only ipsilateral seminal emission. This suggests that some efferent sympathetic signals for emission might run ipsilaterally in humans.     

Does Dopamine Suppress Stress-Induced Intestinal and Renal Vasoconstriction?

Dopamine interference with intestinal and renal sympathetic reflex vasoconstrictor responses was studied in cats anaesthetized with diazepam, fentanyl and nitrous oxide. Vasoconstriction was induced by electric stimulation of the hypothalamic defence-alarm area and by stimulation of somatic and visceral afferents. In addition, intestinal vasoconstriction was elicited by direct stimulation of postganglionic sympathetic efferent nerves. In the intestine, dopamine administration (7.5 microgram X kg-1 X min-1) was not associated with an attenuation of the investigated sympathetic vasoconstrictor responses, although dopamine per se decreased intestinal vascular resistance by 36 +/- 4%. Due to this dopamine-induced background vasodilation, the intestinal blood flow level during stimulation procedures and concomitant dopamine infusion was higher than during similar stimulations prior to dopamine (for defence-alarm area stimulation 45 +/- 16%, for afferent nerve stimulation 79 +/- 22% and for efferent postganglionic nerve stimulation 66 +/- 16%). In the kidney, dopamine per se had only minor effects on vascular resistance and on changes in vascular tone elicited by the stimulation procedures. The renal blood flow level in response to the stimulation procedures was not significantly affected by dopamine. In conclusion, dopamine may contribute to a sustained intestinal blood flow level when administered during supervening stress-related sympathetic activation.     

Effect of dopamine on renal haemodynamics in the denervated dog kidney

Summary The aim of the present study was to explore the potential modulating role of the renal sympathetic nerves in the dopamine-induced vasodilatation in the dog kidney, using the 133-Xenon washout technique.Immediately before and 48 h after combined surgical and local chemical destruction of the sympathetic nerves innervating the left kidney, renal and intrarenal blood flow was monitored in both kidneys. Catecholamine content was determined in control kidneys from untreated dogs, and in the denervated and contralateral, nondenervated kidney 48 h after unilateral sympathectomy.By 48 h after destruction of the sympathetic nerves innervating the left kidney, total renal and particularly cortical flow rates were significantly increased when compared to the right, innervated kidney. Destruction of the sympathetic nerves also resulted in a disappearance of noradrenaline and adrenaline from the kidney and a significant reduction in the content of dopamine in the denervated but an increased level in the innervated kidney.The dopamine-induced increase in renal blood flow was similar in the denervated and in the innervated kidney, suggesting that the sympathetic nerves do not significantly alter the vascular effects of dopamine. The persistence of the dopamine-induced vasodilatation in the sympathectomized kidney supports the concept that dopamine acts directly on postsynaptic, specific dopamine receptors.     

Adenovirus-mediated gene transfer to glomerular cells in newborn mice

The systemic delivery of recombinant adenoviral (rAd) vectors to renal glomeruli has been problematic due to the rapid clearance of the circulating virus by the liver. We have previously shown that prolonged retention of rAd vectors in the circulation by liver bypass improves the transduction of renal glomerular cells in adult mice and rats. This study was done to determine whether newborn mice have a delayed clearance of rAd vectors from the circulation and a more efficient transduction of glomerular cells after a systemic injection of rAd vectors. Newborn (1 day old) and adult (6 months old) C57Bl6/J mice ( n =20 in each group) were injected with rAd vectors carrying the lacZ gene (rAd.lacZ) through the retro-orbital venous plexus (2×10⁹ particles/g body weight). The renal expression of Coxsackie and Adenoviral Receptors (CAR) and lacZ gene were evaluated at different time points by Western blots, immunohistochemistry, -galactosidase staining, enzyme assay activity, and RT-PCR studies in newborn and adult mice. The clearance rate of rAd.lacZ was significantly delayed in newborn mice, and the concentration of circulating virus in these mice was almost ten times higher than that in adult mice. Newborn kidneys showed increased expression of CAR, predominately localized in glomerular cells. These findings were associated with an efficient gene transfer of the lacZ gene into glomeruli and tubules of newborn mice. This study demonstrates for the first time the feasibility of using systemic intravenous injections of rAd vectors to express foreign genes in developing glomeruli of young mice.     

The p75 Neurotrophin Receptor Is Required for the Major Loss of Sympathetic Nerves From Islets Under Autoimmune Attack

Our goal was to determine the role of the p75 neurotrophin receptor (p75NTR) in the loss of islet sympathetic nerves that occurs during the autoimmune attack of the islet. The islets of transgenic (Tg) mice in which β-cells express a viral glycoprotein (GP) under the control of the insulin promotor (Ins2) were stained for neuropeptide Y before, during, and after virally induced autoimmune attack of the islet. Ins2-GP^Tg mice injected with lymphocytic choriomeningitis virus (LCMV) lost islet sympathetic nerves before diabetes development but coincident with the lymphocytic infiltration of the islet. The nerve loss wasmarked and islet-selective. Similar nerve loss, chemically induced, was sufficient to impair sympathetically mediated glucagon secretion. In contrast, LCMV-injected Ins2-GP^Tg mice lacking the p75NTR retained most of their islet sympathetic nerves, despite both lymphocytic infiltration and development of diabetes indistinguishable from that of p75NTR wild-type mice. We conclude that an nducible autoimmune attack of the islet causes a marked and islet-selective loss of sympathetic nerves that precedes islet collapse and hyperglycemia. The p75NTR mediates this nerve loss but plays no role in mediating the loss of islet β-cells or the subsequent diabetes. p75NTR-mediated nerve loss may contribute to the impaired glucose counterregulation seen in type 1 diabetes.     

Neural effects of natural behavior on renal blood flow in spontaneously hypertensive rats

Background In states of stress and exercise, renal blood flow is shown to be depressed, mainly through neural mechanisms. Little is known, however, about the effects of natural or spontaneous behaviors on renal blood flow and renal sympathetic nerve activity. Methods We simultaneously measured renal sympathetic nerve activity and renal blood flow as a Doppler shift during grooming and exploring behaviors in spontaneously hypertensive rats. We also tested the effects of vasodilating drugs on changes in renal blood flow. Results Grooming behavior (n=21) increased renal sympathetic nerve activity, mean arterial pressure, and decreased renal blood flow. Percentage changes in renal sympathetic nerve activity correlated negatively with percentage changes in renal blood flow. Exploring with rearing (n=14) induced similar but larger changes in these variables. Denervation of renal nerves suppressed a reduction in renal blood flow during these behaviors. After intravenous injection of manidipine (a calcium channel blocker) or CV-11974 (an angiotensin II receptor antagonist), the behavior-induced reduction in renal blood flow was significantly smaller than that found before treatment, despite similar increases in renal sympathetic nerve activity. Conclusion Natural behaviors decrease renal blood flow in relation to the enhancement of renal sympathetic nerve activity, which is similar to the responses of the animals to stressful psychologic stimuli. Vasodilating drugs can attenuate the reduction in renal blood flow.     

Evidence for local neural modulation of sympathetic influences on the feline bladder

It is known that resting conditions of bladder volume and pressure influence the response of the cat bladder in situ to sympathetic nerve stimulation. We observed that this was also true when the bladder was decentralized by cutting the sacral spinal roots, the hypogastric nerves, and one sympathetic chain. Under these conditions, elevating intravesical pressure by means of a reservoir of large surface area connected to the bladder resulted in an enhancement of the beta-adrenoceptor-mediated dilatory component of the response to stimulation of either the sympathetic chain or the hypogastric nerves. In order to test whether this enhancement was the result of mechanical or end-organ effects, the change in response to ia isoprenaline was also evaluated. Although the response to isoprenaline was modestly (2-fold) increased at intravesical pressures of 20–30 cm H₂O, the increase in response to hypogastric nerve stimulation (8.5-fold) was significantly greater. The increase in response to sympathetic chain stimulation was intermediate, but only one chain was stimulated. Thus, end-organ or physical factors have some influence on the dilatory response. However, there must be another modulatory component that exerts an effect on the neurally mediated dilatation but not on that produced by isoprenaline. This modulation appears to be activated by bladder distension and to be directed at the nerves, either on their terminals or at the intramural or plexus ganglia. Candidate mechanisms are humoral compounds (e.g., eicosanoids) or a local neural network.     

The functional importance of sympathetic nerves to the liver and endocrine pancreas.

Sympathetic noradrenergic nerves, with their wellknown cardiovascular effects, have recently been found to influence several metabolic and hormone-releasing processes. Morphological investigations in man have revealed a dense sympathetic innervation of the liver parenchyma as well as sympathetic fibers among the endocrine cells in the islets of Langerhans. Functional studies both in animals and man have shown that electrical or reflex activation of the hepatic and pancreatic sympathetic nerve fibers causes an increased output of glucose from the liver as well as a stimulation of glucagon and an inhibition of insulin release from the pancreas. From these results we conclude that damage to sympathetic nerves should be avoided in abdominal surgery.     

Anatomic Study of Periprostatic Nerve Distribution: Immunohistochemical Differentiation of Parasympathetic and Sympathetic Nerve Fibres

Background

Many authors advocate a high anterior incision during nerve-sparing radical prostatectomy (RP) to improve potency results. Despite a growing number of studies describing autonomic nerves in the ventrolateral position of the prostate, little is known about their quality and their role in erectile function.

Objective

The intention of this study was a detailed characterisation of the topographic distribution of periprostatic nerves, including immunohistochemical differentiation of proerectile parasympathetic from sympathetic nerves.

Design, setting, and participants

A total of 228 whole-mount sections of 38 prostates (base, middle, apex) from patients following non–nerve-sparing laparoscopic RP were analysed. Immunohistochemical analysis was performed using antibodies against tyrosine hydroxylase for sympathetic and vesicular acetylcholine transporter for parasympathetic nerve fibre staining.

Outcome measurements and statistical analysis

Quantification of periprostatic parasympathetic and sympathetic nerves was performed after defining prostatic regions via a digital grid. Differences among three independent variables were tested with the nonparametric Kruskal-Wallis test.

Results and limitations

The total number of parasympathetic nerves did not decrease from the base to the apex. They were dispersed at the base and mainly located dorsolaterally at the apex, with 14.6% above the horizontal line at the base and only 1.5% at the apex. In contrast, the total number of sympathetic nerves decreased significantly from base to apex, with a constant proportion of ventrolateral nerves between 9% (base) and 6.2% (apex). This anatomic study is limited by the investigation of postprostatectomy specimens and the lack of functional results.

Conclusions

Despite the presence of ventrolateral periprostatic nerves, only a minority of these nerves seems to have a parasympathetic proerectile quality. The arguments in favour of a high anterior incision during nerve-sparing prostatectomy might not only include preserved nerves but also other factors, such as reduced traction or improved anatomic support of the neural structures.     

Activity of peripheral sympathetic efferent nerves in experimental subarachnoid haemorrhage

The efferent activity of the vertebral, cardiac and renal sympathetic nerves was recorded during the so-called "early vasospasm" period, 25-30 minutes after experimentally induced subarachnoid haemorrhage. Experiments were performed on 51 cats with methods described in Part I of our publication. The animals were held either in a sphynx-like position (Pos. I), or in head-down position (Pos. II), when the level of the cisterna magna was 2-3 cm below the level of the spinal cord, facilitating the injected blood to flow in to, and remain at the base of the brain. According to our results during the "early vasospasm" period, we could not observe such changes in the sympathetic efferent activity, which could be specific for this period. With the gradual decrease in the intracranial pressure, the sympathetic overactivity ceased, and in most cases the level of activity was similar to that of the preinjection period. Our results also indicate that because of the remarkable variability of the activity of the renal sympathetic nerve during the intracranial pressure elevation, recording the activity of one sympathetic nerve only may give misleading results concerning the activity of the whole sympathetic system.     

Seminal emission by electrical stimulation of the spermatic nerve and epididymis

The spermatic nerve and epididymis were stimulated electrically in dogs to elucidate the possibility of artificial seminal emission after bilateral transection of the hypogastric nerves and sympathetic trunks. Before transection, electrical stimulation of a distal end of the severed spermatic nerve caused a trace amount of emission in two dogs and no emission in the remaining four. In contrast, 1 month after the transection, stimulation of a distal end of the severed spermatic nerve caused seminal emission in all six dogs examined, with full seminal volume in four dogs and partial volume in the remaining two. Anatomically, sympathetic nerves originating from the upper portion of the lumbar sympathetic ganglia descended along the spermatic arteries to the testes as spermatic nerves. The present results indicate that spermatic nerves have the potential to generate seminal emission as a compensatory pathway after bilateral transection of the hypogastric nerves. Both direct and percutaneous electrical stimulation of epididymal tails resulted in a full volume of seminal emission in all dogs with transection of both hypogastric nerves and lumbosacral sympathetic trunks as well as in unoperated controls, while high voltage (8 V vs 40-80 V) was required to cause seminal emission by electrical stimulation on the skin surface. Direct stimulation of epididymal tails in men undergoing orchidectomy as treatment for prostatic carcinoma or during biopsy of the contralateral testis in a patient with a testicular tumour, resulted in seminal emission in all five epididymides examined either from the end of the severed vas deferens or in the posterior urethra if the vas deferens was not severed.