title: Penile erectile responses to cavernous nerve stimulation in rats are not affected by nitrate tolerance.
abstract: The aim of this study was to elucidate whether penile erection induced by electrical stimulation of the cavernous nerve was affected in male rats with nitrate tolerance. Nitrate tolerance to nitroglycerin was induced by oral administration of isosorbide dinitrate (ISDN) at 1000 mg/kg to rats, once or twice a day for 5 or 6 days. The rats were anesthetized with sodium pentobarbital 18-24 h after the last dosing with ISDN or its vehicle. Penile erection induced by electrical stimulation was monitored by measuring the penile diameter sonomicrometrically. After measurement of the penile erectile response, nitroglycerin (3-300 microg/kg) was intravenously (i.v.) injected into eight rats treated with the vehicle or ISDN to examine its hypotensive effect. In the vehicle-treated rats, the maximal developed penile diameter (D-max) and the duration of penile erection (T50%, period of time from the maximum erection to its 50% decline) produced by electrical stimulation were 509+/-47 microm and 14.2+/-1.7 s, respectively. On the other hand, neither D-max nor T50% in ISDN-treated rats (509+/-36 microm and 13.1+/-1.3 s, respectively) was different from those in the vehicle-treated rats. However, the hypotensive effects of i.v. injected nitroglycerin were significantly attenuated in the ISDN-treated group as compared with the vehicle-treated group. It is concluded that nitrate tolerance fails to influence penile erection induced by cavernous nerve electrical stimulation in rats.
authors.affiliation: Developmental Pharmacology Research Section, Drug Safety and Disposition Research Laboratories, Eisai Co., Ltd., 1-3, Tokodai 5-Chome, Tsukuba, Ibaraki 300-2635, Japan. h-adachi@hhc.eisai.co.jp
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Adachi
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D009566:Nitrates / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology*; D051381:Rats
chemical_list: D009566:Nitrates; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate