1. The effects of
nitric oxide (NO) releasing substances,
sodium nitroprusside, 3-morpholino sydnonimine (SIN-1) and a novel oxatriazole derivative,
GEA 3162, on blood pressure and heart rate were studied after peripheral or central administration in anaesthetized normotensive Wistar rats. 2. Given as cumulative
intravenous injections, both
nitroprusside and
GEA 3162 (24-188 nmol kg-1) induced short-lasting and dose-dependent decreases in mean arterial pressure, while SIN-1 decreased blood pressure only slightly even after larger doses (94-3000 nmol kg-1). Heart rate increased concomitantly with the hypotensive effect of the NO-releasing substances. 3. Cumulative intracerebroventricular administration of
GEA 3162 (24-188 nmol kg-1) induced a dose-dependent
hypotension with slight but insignificant increases in heart rate. In contrast, intracerebroventricular
nitroprusside induced little change in blood pressure, while a large dose of SIN-1 (3000 nmol kg-1, i.c.v.) slightly increased mean arterial pressure. However, intracerebroventricular
nitroprusside and SIN-1 increased heart rate at doses that did not significantly affect blood pressure. 4. To determine whether the cardiovascular effects of
GEA 3162 were attributable to an elevation of
cyclic GMP levels, pretreatments with
methylene blue, a putative
guanylate cyclase inhibitor, were performed. This substance failed to attenuate the cardiovascular effects of peripherally or centrally administered
GEA 3162, suggesting that the effects were independent of
guanylate cyclase. 5. In conclusion, the centrally administered NO-donor,
GEA 3162, induced a dose-dependent. hypotensive response without significant changes in heart rate. Furthermore, intracerebroventricular
injections of
nitroprusside and SIN-1 increased heart rate without affecting blood pressure. These results suggest that NO released by these drugs may affect central mechanisms involved in cardiovascular regulation independently of
cyclic GMP.