EFFECT OF THE SELECTIVE PHOSPHODIESTERASE TYPE 5 INHIBITOR SILDENAFIL ON ERECTILE FUNCTION IN THE ANESTHETIZED DOG

Abstract

No AccessJournal of UrologyInvestigative Urology1 Jul 1998EFFECT OF THE SELECTIVE PHOSPHODIESTERASE TYPE 5 INHIBITOR SILDENAFIL ON ERECTILE FUNCTION IN THE ANESTHETIZED DOG ANTHONY J. CARTER, STEPHEN A. BALLARD, and ALASDAIR M. NAYLOR ANTHONY J. CARTERANTHONY J. CARTER , STEPHEN A. BALLARDSTEPHEN A. BALLARD , and ALASDAIR M. NAYLORALASDAIR M. NAYLOR View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)63097-0AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The effects of sildenafil, a highly selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, on erectile function in the anesthetized dog were evaluated. Materials and Methods: In pentobarbital-anesthetized dogs, increases in intracavernosal pressure in the corpus cavernosum and penile blood flow were induced by pelvic nerve stimulation over a frequency range of 1 to 16 hertz. The effects of increasing doses of sildenafil on electrically stimulated intracavernosal pressure, penile blood flow, blood pressure, and heart-rate were evaluated. In parallel experiments, the effects of the nitric oxide synthase inhibitor N omega-Nitro-L-Arginine (L-NOArg) on these same parameters also were assessed. Results: The effects of nerve stimulation on intracavernosal pressure and blood flow to the penis were blocked by L-NOArg, 0.1-3 mg./kg., in a dose-related manner, confirming the important role of nitric oxide in producing erections. Sildenafil, 1-100 micro g./kg administered intravenously, had no direct effect on intracavernosal pressure but potentiated the increase in intracavernosal pressure induced by nerve stimulation. This potentiation occurred at sildenafil plasma concentrations consistent with its relaxation effect on isolated human cavernosal tissue and its inhibition of phosphodiesterase type 5 in vitro. Sildenafil had no significant effect on blood pressure or heart rate. Conclusions: By inhibiting cyclic guanosine monophosphate-specific phosphodiesterase type 5, sildenafil augments the neuronal mechanism responsible for penile erection. This mechanism explains the significant improvements reported in the rigidity and duration of erections seen in patients with erectile dysfunction who have been treated with oral sildenafil. References 1 : The investigation of impotence.. Br. J. Urol.1991; 68: 449. Google Scholar 2 : Impotence. Int. J. Impotence Res.1993; 5: 181. Google Scholar 3 : Pharmacological management of erectile dysfunction.. Drugs1995; 50: 465. Google Scholar 4 : Clinical guidelines on erectile dysfunction: summary report on the treatment of organic erectile dysfunction. J. Urol.1996; 156: 2007. Abstract, Google Scholar 5 : Role of nitric acid in the physiology of erection. Biol. Reprod.1995; 52: 485. 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Google Scholar Discovery Biology Department, Pfizer Central Research, Sandwich, United Kingdom© 1998 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited ByPrieto D, Rivera L, Recio P, Rubio J, Hernández M and García-Sacristán A (2018) Role of Nitric Oxide in the Relaxation Elicited by Sildenafil in Penile Resistance ArteriesJournal of Urology, VOL. 175, NO. 3, (1164-1170), Online publication date: 1-Mar-2006.MIZUSAWA H, HEDLUND P, BRIONI J, SULLIVAN J and ANDERSSON K (2018) Nitric Oxide Independent Activation of Guanylate Cyclase by YC-1 Causes Erectile Responses in the RatJournal of Urology, VOL. 167, NO. 5, (2276-2281), Online publication date: 1-May-2002.BISCHOFF E, NIEWOEHNER U, HANING H, SAYED M, SCHENKE T and SCHLEMMER K (2018) THE ORAL EFFICACY OF VARDENAFIL HYDROCHLORIDE FOR INDUCING PENILE ERECTION IN A CONSCIOUS RABBIT MODELJournal of Urology, VOL. 165, NO. 4, (1316-1318), Online publication date: 1-Apr-2001.DOHERTY P, BIVALACQUA T, CHAMPION H, KADOWITZ P, MEERVELD B, BERZETEI-GURSKE I and HELLSTROM W (2018) DIRECT EFFECTS OF SELECTIVE TYPE 5 PHOSPHODIESTERASE INHIBITORS ALONE OR WITH OTHER VASODILATORS ON THE ERECTILE RESPONSE IN CATSJournal of Urology, VOL. 165, NO. 3, (1004-1009), Online publication date: 1-Mar-2001.GEMALMAZ H, WALDECK K, CHAPMAN T, TUTTLE J, STEERS W and ANDERSSON K (2018) IN VIVO AND IN VITRO INVESTIGATION OF THE EFFECTS OF SILDENAFIL ON RAT CAVERNOUS SMOOTH MUSCLEJournal of Urology, VOL. 165, NO. 3, (1010-1014), Online publication date: 1-Mar-2001.ANDERSSON K, GEMALMAZ H, WALDECK K, CHAPMAN T, TUTTLE J and STEERS W (2018) THE EFFECT OF SILDENAFIL ON APOMORPHINE-EVOKED INCREASES IN INTRACAVERNOUS PRESSURE IN THE AWAKE RATJournal of Urology, VOL. 161, NO. 5, (1707-1712), Online publication date: 1-May-1999. Volume 160Issue 1July 1998Page: 242-246 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.MetricsAuthor Information ANTHONY J. CARTER More articles by this author STEPHEN A. BALLARD More articles by this author ALASDAIR M. NAYLOR More articles by this author Expand All Advertisement PDF DownloadLoading ...