Characterization of nitrergic function in monkey penile erection in vivo and in vitro

Abstract

The nitrergic nerve appears to have a major role in the neuronal regulation of penile erection. Cholinergic innervation has been shown histochemically in penile cavernous tissues, but its functional role is not well understood. This study was aimed at examining the functional properties of the nitrergic nerve and the possible involvement of cholinergic function in the regulation of monkey penile erection in vivo and in vitro. In anesthetized Japanese monkeys, electrical stimulation of the cavernous nerve caused a frequency-dependent increase in intracavernous pressure and penile erection, and atropine enhanced the pressure response. Intravenous injections of N G -nitro-L-arginine (L-NA) markedly inhibited the stimulation-induced pressure increase and the erectile response, and L-arginine partially restored the pressure response. In some monkeys, the intracavernous pressure increase caused by nerve stimulation was reversed by treatment with L-NA; however, L-arginine restored the pressor response. In addition, hexamethonium suppressed the pressure increase that resulted from the nerve stimulation. In corpus cavernosum isolated from monkeys, transmural electrical stimulation elicited frequency-dependent relaxation. The relaxation was attenuated by physostigmine, and was potentiated by atropine. Relaxation was markedly inhibited by treatment with L-NA. It appears that nitric oxide (NO) released from inhibitory nerves, even at low frequencies, has a pivotal role in the initiation and maintenance of intracavernous pressure increase and penile erection in monkeys. Prejunctional muscarinic receptors in nitrergic nerves are expected to participate in the impairment of NO release. Nitrergic nerves responsible for penile erection may originate from ganglia close to the corpus cavernosum. INTRODUCTIONThe function of nitric oxide (NO) as a neurotransmitter in nonadrenergic, noncholinergic nerves responsible for penile erection was first determined in the corpus cavernosum isolated from rabbits. 1 The presence of NO-synthase-containing nerve fibers in the corpora cavernosa and the involvement of NO in the intracavernous pressure increase by electrical stimulation of the cavernous nerve in anesthetized rats were outlined by Burnett et al. 2 The role of neurogenic NO in penile erection has been shown in a variety of experimental animals. [3][4][5] Involvement of the NO-cyclic GMP pathway in the relaxation of human corpus cavernosum strips in response to electrical field stimulation has also been shown. 6-9 Efficacy of phosphodiesterase-5 inhibitors in patients with erectile dysfunction supports the idea that cyclic GMP formed by NO-mediated activation of guanylyl cyclase has an important role in penile tumescence. 10 Recent studies suggest that NO released from the sinusoidal endothelium is also involved in the maintenance of penile erection. 11 Although cholinergic innervation has been shown in the penile corpus cavernosum, the functional role has not been elucidated. 12,13 Furthermore, reports in the literature have revealed...

nNOS-positive minor-branches of the dorsal penile nerves is associated with erectile function in the bilateral cavernous injury model of rats

“…The mechanism of the human erection requires the coordination of intact neuronal systems, including the CNs, the DPNs and the perineal nerves. In anesthetized Japanese monkeys, electrical stimulation of the CNs caused increased ICP and penile erection, and atropine enhanced the pressure response 35 . Multiple pathways have been proposed for the course of adrenergic fibers to the penis.…”

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…In isolated CC cells, carbachol consistently produces contraction. This means that relaxation induced by ACh can be produced either by inhibition of the release of contractant factors (e.g., NA) and/or by the release of relaxation-producing factors (e.g., NO) (Ayajiki et al, 2009). …”

Cyclic AMP-dependent phosphorylation of neuronal nitric oxide synthase mediates penile erection

“…Neuronal depolarizationinduced production of NO reflects calcium entry activating calmodulin associated with nNOS to stimulate NO formation (8,9). This activation is short-lived and thus is believed to account only for the initiation of penile erection (10,11). Sessa and colleagues (12) established that increased blood flow and associated shear stress, acting via PI3-kinase, augments the activity of the serine protein kinase Akt, which phosphorylates vascular endothelial NOS (eNOS) at serine(S)1179, causing prolonged NO formation at resting intracellular calcium levels (13).…”