VASODILATOR EFFECT AND TOLERANCE INDUCED BY THE NITROCOMPOUND SIN-1 IN RABBIT FEMORAL-ARTERY

The aim of this study was to investigate vascular action of SIN-1 in c omparison with those of other nitrovasodilators in rabbit femoral arte ries. SIN-1 induced relaxations that were unaltered by endothelium rem oval, inhibition of nitric oxide (NO) synthase and inhibition of the f ormation of oxygen reactive species such as anion superoxide, hydrogen peroxide and hydroxyl radical. Oxyhemoglobin reduced the relaxation c aused by SIN-1 and exogenous NO. Exogenous NO and nitroglycerin relaxa tions were endothelium-independent. However, those produced by sodium nitroprusside were increased in endothelium denuded segments. Preincub ation of segments with nitroglycerin (100 mM) produced a marked tolera nce, whereas this effect did not occur when preincubation was done wit h SIN-1 (100 mM). To analyze the in vivo tolerance, rabbits were chron ically treated sin SIN-1 or nitroglycerin (15 mg/kg every 8 h, s.c.). Chronic treatment with SIN-1 for 5 days did not reduce relaxation resp onse. However, 3 days of treatment with nitroglycerin induced a marked reduction of relaxations. Chronic treatment with nitroglycerin did no t modify the relaxation caused by SIN-1, i.e., there was no cross-tole rance between the two drugs. These results suggest that the endotheliu m-independent relaxation elicited by SIN-1 is not modulated by endothe lial NO or free radicals, and does not produce tolerance after its pro longed administration as occurs with nitroglycerin.