Sildenafil augments pelvic nerve‐mediated female genital sexual arousal in the anesthetized rabbit

Min, Kweon Sik; Kim, N N; McAuley, Iain; Stankowicz, M; Goldstein, Irwin; Traish, Abdul

doi:10.1038/sj.ijir.3900610

Cited by 49 publications

(32 citation statements)

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“…In addition, a frequency-dependent response to pelvic nerve stimulation has been documented. 13 These observations suggest that increased genital blood¯ow is mediated by pelvic nerve stimulation and are consistent with data reported by Park et al 10 The effects of several vasoactive agents and the phosphodiesterase type 5 inhibitor sildena®l were studied. Following pelvic nerve stimulation, the tissue hemoglobin content of the genital tissues increased signi®cantly after intravenous injection of sildena®l compared with control.…”

Section: Results From In Vivo Animal Studiessupporting

confidence: 79%

“…In addition, the duration of the increased blood¯ow response was signi®cantly prolonged following sildena®l administration compared with saline. 13 These data suggest that the NO-cGMP pathway is involved in the physiological mechanism of female genital sexual arousal, and, further, that sildena®l facilitates female genital sexual arousal.…”

Section: Results From In Vivo Animal Studiesmentioning

confidence: 91%

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Experimental models for the investigation of female sexual function and dysfunction

et al. 2001

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There have been limited anatomic and physiological investigations of the female sexual arousal response. A broader understanding of the physiologic mechanisms of female sexual arousal function is required to improve the management of women with sexual dysfunction. Three experimental test systems have been developed to understand better the biochemical and physiological mechanisms of female sexual arousal response. An in vivo animal model was developed to record physiological and hemodynamic changes in the clitoris and vagina following pelvic nerve stimulation and administration of vasoactive agents and physiological modulators. In vitro organ baths of clitoral and vaginal tissue were utilized to investigate mechanisms involved in the regulation of smooth muscle contractility. In addition, primary cell cultures of human and animal clitoral and vaginal smooth muscle cells were developed to investigate signal transduction pathways modulating smooth muscle tone. In vivo studies revealed hemodynamic changes in vagina and clitoris in response to pelvic nerve stimulation, vasodilators and physiological modulators. Organ bath studies have demonstrated that clitoral and vaginal smooth muscle tone is affected by non-adrenergic and non-cholinergic neurotransmitters, and the presence of functional alpha 1 and alpha 2 adrenergic receptors in these tissues has been established through biochemical studies. These changes are regulated by the tone of vascular and non-vascular smooth muscle in the vagina and clitoris. Primary cell culture studies have suggested that several physiological modulators such as vasoactive intestinal polypeptide (VIP), nitric oxide (NO), and prostaglandin E (PGE) regulate vaginal smooth muscle contractility. Data from experimental models have provided a preliminary understanding of the mechanisms of the female sexual arousal response.

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Section: Results From In Vivo Animal Studiessupporting

confidence: 79%

Section: Results From In Vivo Animal Studiesmentioning

confidence: 91%

Experimental models for the investigation of female sexual function and dysfunction

et al. 2001

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“…16 PDE5 inhibitors have been implicated for the treatment of FSAD. 17 Our study showing a functional role of nitrergic neurotransmission in the human clitoral corpus cavernosum further supports this view.…”

Section: Nitrergic Neurotransmission In Human Clitoris Sm Creighton Esupporting

confidence: 75%

Functional evidence for nitrergic neurotransmission in a human clitoral corpus cavernosum: a case study

et al. 2003

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Although the presence of neuronal nitric oxide synthase (nNOS) has been demonstrated in human clitoral corpus cavernosum, functional evidence for the nitrergic neurotransmission as a nonadrenergic noncholinergic (NANC) transmitter has been limited to animal studies. Here we show that electrical field stimulation elicited reproducible NANC relaxation responses in a clitoral corpus cavernosum, obtained from a 38-y-old woman undergoing clitoral reduction surgery. These relaxation responses were abolished by an inhibitor of NO synthase or tetrodotoxin proving that they were nitrergic in nature and neuronal in origin. Large and small calibre nitrergic nerves were demonstrated with immunohistochemistry using nNOS antibody, which were also immunostained with cholinergic nerve markers. nNOS expression was confirmed using Western blotting. This is the first report to show that NO produced by nNOS within the cholinergic-nitrergic nerves is responsible for the NANC relaxation responses in a human clitoral corpus cavernosum.

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“…7 The results of the present study support the hypothesis that NO/cGMP plays a significant role in the regulation of vaginal and clitoral blood flow changes in response to neurogenic stimulation in 19 to potentiate neurogenic relaxation of rabbit clitoral smooth muscle 5,6 and to potentiate the increase of rabbit genital blood flow in response to pelvic nerve stimulation. 20 In this study, vardenafil was able to potentiate the vascular sexual response in clitoris and vagina 20 min after intravenous administration, with the effect lasting at least 80 min afterwards, raising the possibility of a wide therapeutic window.…”

Section: Discussionmentioning

confidence: 98%

Vardenafil enhances clitoral and vaginal blood flow responses to pelvic nerve stimulation in female dogs

Angulo

Cuevas

et al. 2003

Int J Impot Res

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The relaxation of the smooth muscle in the vagina and clitoris and the increase of blood flow into these organs is thought to be essential in the female sexual response. Vardenafil is a type 5 phosphodiesterase (PDE5) inhibitor that potentiates the nitric oxide (NO)/cGMP pathway facilitating penile smooth muscle relaxation and improving penile erection in men. Although the potentiation of the NO/cGMP pathway through PDE5 inhibitors can clearly enhance blood flow into the penis and is used in the therapy of male sexual dysfunction, there is controversy about the efficacy of these agents in improving female sexual function. The aim of this work was to evaluate the effects of vardenafil on the increase of blood flow into the vagina and clitoris induced by pelvic nerve electrical stimulation (PNES) in a female dog model. Application of PNES produced consistent and frequency-related increased blood flow into the vagina and clitoris of anesthetized female dogs. The magnitude and duration of the blood flow responses to PNES were variable among the different animals but remained stable over time within the same animal. The intravenous administration of vardenafil (1 mg/kg) significantly potentiated the increases in blood flow produced by PNES into the vagina (381.4 and 206.2% of control response at 5 and 10 Hz, respectively, Po0.01, n ¼ 6) and clitoris (379.4 and 238.5% of control response at 5 and 10 Hz, respectively, Po0.01, n ¼ 6) 20 min after administration. The significant enhancement of PNESinduced responses was maintained 50 min (224.5 and 181.0%, Po0.01 in vagina; 294.8 and 258.9%, Po0.05 in clitoris) and 80 min after vardenafil administration (209.5 and 156.9%, Po0.05 in vagina; 268.9 and 194.9%, Po0.05 in clitoris). Here we present a feasible model for research into female sexual function. Our results show that vardenafil effectively potentiates the blood flow responses to PNES in the genitalia of female dogs. These results emphasize the role of the NO/cGMP pathway in the local vasodilatory response in female sexual organs and provide a rationale for testing PDE5 inhibitors, such as vardenafil, as a treatment for certain forms of female sexual dysfunction.

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Sildenafil augments pelvic nerve‐mediated female genital sexual arousal in the anesthetized rabbit

Cited by 49 publications

References 3 publications

Experimental models for the investigation of female sexual function and dysfunction

Experimental models for the investigation of female sexual function and dysfunction

Functional evidence for nitrergic neurotransmission in a human clitoral corpus cavernosum: a case study

Vardenafil enhances clitoral and vaginal blood flow responses to pelvic nerve stimulation in female dogs

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