EFFECTS OF LONG-TERM TREATMENT WITH ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR ON ANGIOTENSIN-II AND PROSTACYCLIN RELEASE FROM MESENTERIC-ARTERIES IN SPONTANEOUSLY HYPERTENSIVE RATS

To evaluate the long-term effects of an angiotensin-converting enzyme inhibitor (ACEI) on vascular angiotensin II (AII), eicosanoid producti on and vascular reactivities, we treated spontaneously hypertensive ra ts (SHR) with alacepril for 6 weeks and perfused the isolated mesenter ic arterial bed which contains resistance vessels, Alacepril significa ntly lowered the arterial blood pressure, Changes in perfusion pressur e in response to norepinephrine (NE) were attenuated, and isoprotereno l-stimulated AII release from the perfused mesenteric arterial beds wa s inhibited in the alacepril-treated SHR, Vasodilation induced by acet ylcholine (Ach) and prostacyclin (PGI(2)) release was significantly in creased in the vasculature of the alacepril-treated SHR, Alacepril exe rted no effect on cyclic GMP (cGMP) formation, but increased cAMP form ation in the vasculature, These findings suggest that ACEI inhibits AI I formation and facilitates PGI(2) production in the resistance vessel s, which leads to blunting of the presser response to NE and improveme nt of endothelial function in SHR, These humoral and mechanical change s in the vasculature may contribute to the depressor and organ protect ive effects of ACEI.