Elsevier

Brain Research

Volume 825, Issues 1–2, 17 April 1999, Pages 14-21
Brain Research

Research report
Influence of denervation on neurogenic inhibitory response of corpus cavernosum and nitric oxide synthase histochemistry

https://doi.org/10.1016/S0006-8993(99)01204-4Get rights and content

Abstract

Aims of this study were to functionally and histologically determine the localization of ganglia that distribute inhibitory nerves to the penile corpus cavernosum in dogs. In isolated corpus cavernosa from seven control dogs contracted with endothelin-1, transmural electrical stimulation (5 Hz for 40 s) elicited contractions which were reversed to relaxations by prazosin. The relaxation was abolished by NG-nitro-l-arginine (l-NNA), a nitric oxide (NO) synthase inhibitor, and restored by l-arginine. Parts of bilateral pelvic nerve plexuses running to the penis were surgically denervated in anesthetized three dogs, or the bilateral neuronal tissues close to the corpus cavernosum were removed for denervation in seven dogs. One week after the operation, the dogs were sacrificed. Denervation of pelvic plexus did not attenuate neurogenic relaxations, whereas denervation of the distal portion abolished the responses. In the tissues close to the corpus cavernosum excised for denervation, ganglia containing abundant nerve cells and fibers stained by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase method were histochemically detected. One week after the denervation, there were no NADPH diaphorase-positive nerve fibers in the trabecula of corpus cavernosum. It is concluded that neurogenic relaxations of canine corpus cavernosum are mediated by NO synthesized from l-arginine in nerve terminals, and this nerve is originated from ganglia located close to the corpus cavernosum but not directly from the pelvic nerve plexus.

Introduction

Non-adrenergic, non-cholinergic inhibitory innervation has been reported in blood vessels, gastrointestinal tract, corpus cavernosum and smooth muscle of other organs [19]. On the basis of discovery of substances inhibiting NO synthase activity [11], NO has been determined to be a key molecule mediating neurogenic relaxations, in particular in cerebral arteries [16]and corpus cavernosum [3]. Electrical stimulation of the pelvic nerve plexus increases pressures of the corpus cavernosum, leading to the penile erection. Although vasoactive intestinal polypeptide (VIP) and acetylcholine released from nerve terminals have been considered to mediate the responses, recent studies on rats, rabbits and dogs suggest the importance of NO on the basis of findings that the response to nerve stimulation is not influenced by atropine or VIP antagonists but abolished by NO synthase inhibitors 1, 2, 3, 9, 18. In the isolated corpus cavernosum from dogs electrical nerve stimulation induces relaxations which are abolished by NG-nitro-l-arginine (l-NNA), a NO synthase inhibitor and restored by l-arginine [8]. Electrical stimulation elicits relaxation and increase the cyclic GMP content in the cavernous strips, the responses being abolished by treatment with l-NNA [10]. These findings indicate that NO plays a quite important role in increasing the intracavernous pressure and evoking the penile erection. NO synthase-containing ganglia are located at the base of the prostate, and cavernous nerve extending to the penis is stained for NO synthase in humans [4]. However, functional roles of the ganglia have not been determined. Histological demonstration of innervation does not always reflect the functional significance, as seen in corpus cavernosum in which cholinergic and VIPergic nerves histologically determined fail to alter the cavernous muscle tone and pressure.

Because pressor responses to electrical stimulation of the pelvic nerve plexus of corpus cavernosum are abolished by treatment with hexamethonium [2], we have hypothesized that the ganglion is present distal to the site of electrical stimulation in dogs. Therefore, the present study was undertaken to determine the ganglia containing NO synthase-positive nerve cells and fibers near or in the canine corpus cavernosum and to clarify functioning of the ganglia by the use of cavernous strips obtained from control dogs and those subjected to surgical denervation.

Section snippets

Preparation

Seventeen male mongrel dogs, weighing 7 to 13 kg, were used for these experiments. They were bred in the Institute of Experimental Animals, Shiga University of Medical Science. The Animal Care and Use Committee of Shiga University of Medical Science approved the use of dogs in this study. They were anesthetized with intravenous injections of sodium pentobarbital (30 mg/kg) and killed by bleeding from the carotid arteries. In three dogs under pentobarbital anesthesia, the parts of pelvic nerve

Mechanical response to transmural electrical stimulation, nitric oxide and nicotine

In strips of the corpus cavernosum from control dogs partially contracted with endothelin-1, transmural electrical stimulation (5 Hz) induced a contraction which was reversed to a relaxation by treatment with prazosin (10−5 M). In the cavernous strips from dogs in which parts of pelvic nerve plexuses running to the penis were bilaterally excised a week ago, the mechanical responses to electrical stimulation were not appreciably altered (50.0±16.5% relaxation, n=3), as compared with those seen

Discussion

Bilateral denervation of parts of the pelvic nerve plexuses running to the penis did not alter the relaxant response to electrical nerve stimulation of corpus cavernosum strips isolated from dogs one week after the operation. However, removal of neuronal tissues close to the corpus cavernosum abolished the neurogenic relaxant response of cavernous strips. In the strips obtained from dogs that were treated with prazosin, relaxations induced by nerve stimulation were abolished by l-NNA but not by

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