EFFECT OF INTRACEREBROVENTRICULAR AND INTRAVENOUS ADMINISTRATION OF NITRIC-OXIDE DONORS ON BLOOD-PRESSURE AND HEART-RATE IN ANESTHETIZED RATS

1 The effects of nitric oxide (NO) releasing substances, sodium nitrop russide, 3-morpholino sydnonimine (SIN-1) and a novel oxatriazole deri vative, GEA 3162, on blood pressure and heart rate were studied after peripheral or central administration in anaesthetized normotensive Wis tar rats. 2 Given as cumulative intravenous injections, both nitroprus side and GEA 3162 (24-188 nmol kg(-1)) induced short-lasting and dose- dependent decreases in mean arterial pressure, while SIN-1 decreased b lood 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 adm inistration 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, intracerebrove ntricular nitroprusside and SIN-1 increased heart rate at doses that d id 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 gu anylate cyclase inhibitor, were performed. This substance failed to at tenuate the cardiovascular effects of peripherally or centrally admini stered GEA 3162, suggesting that the effects were independent of guany late cyclase. 5 In conclusion, the centrally administered NO-donor, GE A 3162, induced a dose-dependent hypotensive response without signific ant changes in heart rate. Furthermore, intracerebroventricular inject ions of nitroprusside and SIN-1 increased heart rate without affecting blood pressure. These results suggest the NO released by these drugs may affect central mechanisms involved in cardiovascular regulation in dependently of cyclic GMP.