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 production and vascular reactivities, we treated spontaneously hypertensive rats (SHR) with alacepril for 6 weeks and perfused the isolated mesenteric arterial bed which contains resistance vessels. Alacepril significantly lowered the arterial blood pressure. Changes in perfusion pressure in response to norepinephrine (NE) were attenuated, and isoproterenol-stimulated AII release from the perfused mesenteric arterial beds was inhibited in the alacepril-treated SHR. Vasodilation induced by acetylcholine (Ach) and prostacyclin (PGI2) release was significantly increased in the vasculature of the alacepril-treated SHR. Alacepril exerted no effect on cyclic GMP (cGMP) formation, but increased cAMP formation in the vasculature. These findings suggest that ACEI inhibits AII formation and facilitates PGI2 production in the resistance vessels, which leads to blunting of the pressor response to NE and improvement of endothelial function in SHR. These humoral and mechanical changes in the vasculature may contribute to the depressor and organ protective effects of ACEI.
Ito
M
M
Second Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Soma
M
M
Izumi
Y
Y
Kanmatsuse
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000096:biosynthesis* / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011464:Epoprostenol / Q000096:biosynthesis* / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D002216:Captopril; D011464:Epoprostenol; D007545:Isoproterenol; D000109:Acetylcholine; C046835:alacepril; D009638:Norepinephrine