Sildenafil relaxes rabbit clitoral corpus cavernosum

Vemulapalli, Subbarao; Kurowski, Stanley

doi:10.1016/s0024-3205(00)00596-8

Cited by 47 publications

(29 citation statements)

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“…17,18 Furthermore, the NO/cGMP pathway has been reported to mediate the neurogenic relaxation of the rabbit clitoral corpus cavernosum and vagina. 5,6 In the latter tissue, an additional unidentified neurotransmitter is also involved. 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.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 In the latter tissue, an additional unidentified neurotransmitter is also involved. 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: 99%

“…[2][3][4] Although the neurogenic control of the vascular events in these tissues has not been thoroughly investigated, it is known that the nitric oxide (NO)/cGMP pathway mediates the neurogenic relaxation of rabbit clitoral corpus cavernosum and is involved in the neurogenic relaxation of rabbit vagina. [5][6][7] Vardenafil is a potent and selective type 5 phosphodiesterase (PDE5) inhibitor that enhances NO-mediated relaxation of human corpus cavernosum and NO-induced rabbit penile erection, and it has been reported to potentiate erectile function in patients. 8,9 Furthermore, vardenafil is currently under clinical investigation for the treatment of erectile dysfunction (ED).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…7 Furthermore, these nitrergic responses were potentiated with PDE5 inhibitors zaprinast 7 and sildenafil. 10 Expression of nNOS in the nerve fibres within the human clitoral corpus cavernosum has been demonstrated. 7 More recently, PDE5 inhibitor vardenafil has been shown to enhance clitoral blood flow response to pelvic nerve stimulation in anaesthetised dog.…”

Section: Discussionmentioning

confidence: 99%

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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“…Second messenger systems involved in the contraction of both vaginal and clitoral 41,42 tissues have been assessed using in vitro tissue baths. Isolated strips of contractile tissue allow for the assessment of the responsiveness to chemical mediators and downstream messengers involved in the dilation and contraction without compensatory mechanisms that are present in the whole animal.…”

Section: Isolated Tissues and Cellsmentioning

confidence: 99%

A framework for the present and future development of experimental models of female sexual dysfunction

2003

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Female sexual dysfunction (FSD) is currently categorized according to disorders of (i) desire, (ii) arousal, (iii) orgasm and (iv) sexual pain. The advancement of research defining the physiological, pathophysiological and psychological mechanisms of these disorders, and to develop treatments for FSD, has been hampered by the paucity of experimental paradigms and animal models. It may be that animal models of FSD are best suited to address arousal disorders that include persistent or routine inability to attain or maintain genital lubrication or engorgement. Although still limited in scope, experimental models of FSD have involved a range of in vitro to in vivo methodologies. Specifically, the in vitro and in situ models include vaginal or clitoral smooth muscle preparations, histological evaluation and vaginal blood flow assessments. Previously, in vivo studies of sexual responses focussed on behavioral paradigms involving lordotic posturing and receptivity, as well as indices of motivation using a dual chamber pacing method. Recently, a new model of female sexual arousal was developed using pharmacological CNS stimulation; responses that were found to be sensitive to cardiovascular status, aging and hormonal conditions. It is important that a wide variety of animal models continue to be developed to reflect the multifactorial basis of the condition.

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Sildenafil relaxes rabbit clitoral corpus cavernosum

Cited by 47 publications

References 0 publications

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

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

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

A framework for the present and future development of experimental models of female sexual dysfunction

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