NO DEVELOPMENT OF TOLERANCE TO THE HYPOTENSIVE EFFECT OF KRN2391, A NOVEL VASODILATOR CONTAINING A NITRATE MOIETY

The present studies were performed to examine whether tolerance develo ps to the hypotensive effects of KRN2391, yano-N'-(2-nitroxyethyl)-3-p yridinecarboximidamide monomethanesulfonate. Rats were administered KR N2391 (0.3 or 1 mg/kg, s.c.) or nitroglycerin (10 mg/kg, s.c.) three t imes a day for 1 to 8 days and blood pressure was then measured under anesthesia. Chronic pretreatment with nitroglycerin attenuated the dec rease in blood pressure induced by i.v. nitroglycerin but not that by i.v. KRN2391. Chronic pretreatment with KRN2391 (0.3 or 1 mg/kg, s.c.) had no effect on the decreases in blood pressure induced by i.v. nitr oglycerin or i.v. KRN2391. It can be concluded that, in this rat model , no tolerance develops to the hypotensive effects of KRN2391.