Nitric Oxide-Cyclic GMP Signaling Pathway in the Regulation of Rabbit Clitoral Cavernosum Tone¹

Abstract

We investigated the role of nitric oxide (NO)-guanosine 3′,5′-cyclic monophosphate (cGMP) signaling in the regulation of rabbit clitoral cavernosum (CC) tone. Tension measurements, reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and NADPH-diaphorase staining were performed in CC. In the precontracted CC strips with phenylephrine (10–5 M), acetylcholine (ACh) relaxed, dependent on dosage. Pretreatment with atropine, Nω nitro-l-arginine-methyl ester (NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), guanylate cyclase inhibitor abolished the ACh-induced relaxations, but tetrodotoxin (TTX) did not. Sodium nitroprusside relaxed the strips in the presence of atropine and NAME, but not in the presence of ODQ. Electrical field stimulation (EFS) relaxed the strips dependent on stimulus strength. Pretreatment with TTX, NAME, or ODQ abolished the EFS-induced relaxation, but atropine did not. l-Arginine partially restored the inhibited response to ACh and EFS. The inducible NO synthase (iNOS) and neuronal NOS (nNOS) mRNAs and iNOS and endothelial NOS (eNOS) proteins were identified in the CC. NADPH-diaphorase staining revealed the positivity on the nerve trunks and fine nerve fibers in the CC. Finally, results demonstrate that the nNOS, ENOS, and the NO-cGMP signaling pathway are involved in the regulation of clitoral tumescence.

The neurovascular mechanism of clitoral erection: nitric oxide and cGMP‐stimulated activation of BKCachannels

“…Nitrergic nerves (4) and, more specifically, NO and cGMP (29), have been shown to cause relaxation in rabbit clitoral corpus cavernosum. These meticulous studies showed that EFS induces nitrergic relaxation responses by a mechanism that is inhibited by TTX, ODQ, and L-NAME.…”

Physiology of Female Sexual Function: Animal Models

“…The role of the NO/cGMP system in clitoral erection is further indicated by in vitro animal experiments. In rabbits, clitoral corpus cavernosum inhibition of NOS dramatically abolishes electrically stimulated relaxation, whereas sildenafil augments the relaxation [27,62,63]. In the human clitoral tissue, sildenafil has been demonstrated to inhibit PDE5 [64], and immunohistochemical studies have identified NOS immunoreactive nerve bundles within the glans and corpora cavernosa of the clitoris [65].…”

Restoration of Female Genital Vasocongestive Arousal Responses in Young and Aged Rats

“…Both the vagina and clitoris have been shown to be abundantly innervated by NO-producing neurons [17,18]. During stimulation at the level of the genitalia, NO has been suggested to mediate, at least in part, smooth muscle relaxation via a cyclic guanosine monophosphate-dependent mechanism [19].…”

“…While the physiology of a female sexual response has not yet been fully elucidated, evidence to date suggests that nitric oxide (NO) plays a major role, at least in the physiological component of the response [15,16]. Both the vagina and clitoris have been shown to be abundantly innervated by NO-producing neurons [17,18]. During stimulation at the level of the genitalia, NO has been suggested to mediate, at least in part, smooth muscle relaxation via a cyclic guanosine monophosphate-dependent mechanism [19].…”