A Review of the Physiology and Pharmacology of Peripheral (Vaginal and Clitoral) Female Genital Arousal in the Animal Model

No AccessJournal of UrologyArticles1 Aug 2003A Review of the Physiology and Pharmacology of Peripheral (Vaginal and Clitoral) Female Genital Arousal in the Animal Model RICARDO MUNARRIZ, SOO WONG KIM, NOEL N. KIM, ABDULMAGED TRAISH, and IRWIN GOLDSTEIN RICARDO MUNARRIZRICARDO MUNARRIZ , SOO WONG KIMSOO WONG KIM , NOEL N. KIMNOEL N. KIM , ABDULMAGED TRAISHABDULMAGED TRAISH , and IRWIN GOLDSTEINIRWIN GOLDSTEIN View All Author Informationhttps://doi.org/10.1097/01.ju.0000075352.03144.15AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We review contemporary scientific data concerning the physiology and pharmacology of peripheral female genital arousal responses in the animal (rabbit and rat) model. Materials and Methods: We reviewed the contemporary literature and our research studies concerning physiology and pharmacology of peripheral genital arousal from 3 experimental animal models, including genital smooth muscle cell culture, genital strip organ bath and in vivo animal model studies. Results: Nitric oxide (NO) appears to be a key pathway mediating clitoral smooth muscle relaxation. In the vagina NO appeared to have a more controversial role in mediating vaginal muscularis smooth muscle relaxation. Vasoactive intestinal polypeptide induced vaginal smooth muscle relaxation. Functional α-adrenergic receptors were expressed in the clitoris and vagina, and mediated norepinephrine induced genital smooth muscle contraction. Androgens and estrogens modulated distinct physiological responses in vagina, and androgens facilitated vaginal smooth muscle relaxation. Papaverine hydrochloride, a smooth muscle relaxant, and phentolamine mesylate, an α-blocker, administered into the vaginal spongy muscularis layer increased vaginal wall pressure and vaginal blood flow. Sildenafil caused significant increases in genital (clitoral and vaginal) blood flow and vaginal lubrication in intact and ovariectomized animals. This response was more pronounced in animals treated with estradiol, suggesting that the NO cyclic guanosine monophosphate pathway is involved in the physiological mechanism of female genital arousal and that sildenafil facilitates this response in an in vivo animal model. Conclusions: To achieve improved understanding of the biological aspects of female sexual function, further research is needed in the physiology and pharmacology of peripheral (clitoral and vaginal) genital arousal in the animal model. References 1 : Sexual dysfunction in the United States: prevalence and predictors. JAMA1999; 281: 537. Crossref, Medline, Google Scholar 2 : Sex and human female reproductive tract—what really happens during coitus. Int J Impot Res1998; 10: S14. Google Scholar 3 : Aspects of genital physiology and pathology. Semin Neurol1992; 12: 87. Google Scholar 4 : Innervations of vasculature and microvascular of the human vagina by NOS and neuropeptide-containing nerves. A Anat1996; 188: 633. Google Scholar 5 : Vasoactive intestinal polypeptide and the female genital tract: relationship to reproductive phase and delivery. Am J Obstet Gynecol1982; 43: 414. Google Scholar 6 : Vasoactive intestinal peptide as a neurotransmitter in the female genital tract. Am J Obstet Gynecol1983; 147: 208. Google Scholar 7 : Vasoactive intestinal polypeptide (VIP) provokes vaginal lubrication in normal women. Peptides1987; 8: 797. Google Scholar 8 : Vasoactive intestinal polypeptide and human vaginal blood flow: comparison between transvaginal and intravenous administration. J Clin Exp Pharm Physiol1990; 17: 61. Google Scholar 9 : Ephedrine-activated physiological sexual arousal in women. Arch Gen Psychiat1998; 55: 652. Google Scholar 10 : Inhibition of subjective and physiological sexual arousal in women by clonidine. Psychosom Med1997; 59: 399. Google Scholar 11 : The effect of labetalol and propanolol on pressure response to sexual arousal in women. Br J Pharmacol1981; 12: 341. Google Scholar 12 : Characterization of phosphodiesterase activity inhuman clitoral corpus cavernosum smooth muscle cells in culture. Biochem Biophys Res Com1998; 249: 612. Google Scholar 13 : Development of human and rabbit vaginal smooth muscle cultures: effects of vasoactive agents on intracellular levels of cyclic nucleotides. Mol Cell Biol Res Commun1999; 2: 131. Google Scholar 14 : Effects of estrogen withdrawal on nitric oxide synthase expression and apoptosis in the rat vagina. Urology1998; 51: 650. Google Scholar 15 : Nitric oxide synthase in the rabbit uterus and vagina: hormonal regulation and functional significance. Biol Reprod2000; 62: 1387. Google Scholar 16 : Characterization of NOS activity in the rabbit uterus and vagina: down regulation by estrogen. Life Sci1998; 62: 2093. Google Scholar 17 : Role of androgens in female genital arousal: receptor expression, structure and function. Fertil Steril2002; 77: 11. Google Scholar 18 : Biochemical and functional characterization of alpha-adrenergic receptors in rabbit vagina. LIfe Sci2002; 71: 2909. Google Scholar 19 : Nitrergic neurotransmission mediates the non-adrenergic non-cholinergic responses in the clitoral corpus cavernosum of the rabbit. Br J Pharmacol1998; 125: 1627. Google Scholar 20 : Sildenafil relaxes rabbit clitoral corpus cavernosum. Life Sci2000; 67: 23. Google Scholar 21 : Characterization of the non-nitrergic NANC relaxation responses in the rabbit vaginal wall. Br J Pharmacol2002; 135: 546. Google Scholar 22 Kim N.N., Min K., Pessina M., Munarriz R., Goldstein I., Traish A.M.: Effects of ovariectomy and steroid hormones on vaginal muscle contractility. Unpublished data Google Scholar 23 : Effects of diabetes on neurotransmission in the rat vaginal smooth muscle. Int J Impot Res2001; 13: 58. Google Scholar 24 : Vasculogenic female sexual dysfunction: the hemodynamic basis for vaginal engorgement insufficiency and clitoral erectile insufficiency. Int J Impot Res1997; 9: 27. Google Scholar 25 : Increases in clitoral and vaginal blood flow following clitoral and pelvic plexus nerve stimulations in the female rat. Int J Impot Res2000; 12: 53. Google Scholar 26 : Vaginal physiological changes in a model of arousal in anesthetized rats. Am J Physiol Regul Integr Comp Physiol2001; 281: R140. Google Scholar 27 : Hemodynamic evaluation of the female sexual arousal response in an animal model. J Sex Marital Ther2001; 27: 557. Google Scholar 28 : Effects of ovariectomy and estrogen and androgen treatment on sildenafil-mediated changes in female genital blood flow and vaginal lubrication in the animal model. Am J Obstet Gynecol2002; 187: 1370. Google Scholar 29 : Systemic administration of apomorphine improves the hemodynamic mechanism of clitoral and vaginal engorgement in the rabbit. Int J Impot Res2000; 12: 235. Google Scholar 30 : Decreased circulating levels of estrogen alter vaginal and clitoral blood flow and structure in the rabbit. Int J Impot Res2001; 13: 116. Google Scholar 31 : Effects of ovariectomy and estrogen replacement on basal and pelvic nerve stimulated vaginal lubrication in an animal model. J Sex Marital Ther2003; 29: 77. Google Scholar 32 : Effects of estrogen on nitric oxide synthase and histological composition in the rabbit clitoris and vagina. Int J Impot Res2001; 13: 205. Google Scholar From the Institute for Sexual Medicine, Department of Urology, Boston University School of Medicine, Boston, Massachusetts© 2003 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byMartin-Alguacil N, Schober J, Kow L and Pfaff D (2018) Arousing Properties of the Vulvar EpitheliumJournal of Urology, VOL. 176, NO. 2, (456-462), Online publication date: 1-Aug-2006.O'CONNELL H, SANJEEVAN K and HUTSON J (2018) ANATOMY OF THE CLITORISJournal of Urology, VOL. 174, NO. 4 Part 1, (1189-1195), Online publication date: 1-Oct-2005. Volume 170Issue 2SAugust 2003Page: S40-S45 Advertisement Copyright & Permissions© 2003 by American Urological Association, Inc.Keywordssex hormonearousalnitric oxidesteroidsgenitalia, femaleMetrics Author Information RICARDO MUNARRIZ More articles by this author SOO WONG KIM More articles by this author NOEL N. KIM More articles by this author ABDULMAGED TRAISH More articles by this author IRWIN GOLDSTEIN More articles by this author Expand All Advertisement PDF downloadLoading ...