Renin inhibitor and converting enzyme inhibitors suppress vascular angiotensin II.
The direct effects of a renin inhibitor, N-acetyl-pepstatin and five angiotensin converting enzyme inhibitors, captopril and the active diacid forms of enalapril, ramipril, cilazapril, and CS-622, on the vascular renin-angiotensin system were examined in isolated perfused rat mesenteric arteries. Vascular renin activity and angiotensin II (Ang II) released into the perfusate were determined. Infusion of N-acetyl-pepstatin (5 X 10(-8)-5 X 10(-6) M) suppressed vascular renin activity and Ang II release dose dependently. Isoproterenol (10(-6) M) induced a 135 +/- 30% increase in Ang II release from the basal value. N-Acetyl-pepstatin (5 X 10(-6) M) suppressed isoproterenol-induced Ang II release. Infusions of 5 X 10(-6) M captopril and the diacid forms of enalapril, ramipril, cilazapril, and CS-622 by themselves had little effect on Ang II release, but concomitant infusion of isoproterenol with these angiotensin converting enzyme inhibitors significantly decreased Ang II release (71 +/- 21%, 51 +/- 40%, 8 +/- 21%, 69 +/- 24%, and 44 +/- 29% increase, respectively, from the basal values). These results indicate that N-acetyl-pepstatin suppresses the vascular renin-angiotensin system. This effect may in part contribute to the hypotensive actions of renin inhibitors. Although angiotensin converting enzyme inhibitors also suppress locally generated Ang II, the mechanism and physiological significance still remain to be clarified.
Saito
H
H
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Nakamaru
M
M
Ogihara
T
T
Rakugi
H
H
Kumahara
Y
Y
Shimamoto
K
K
Miyazaki
M
M
Inagami
T
T
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D010436:Pepstatins / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects; D000092502:Renin Inhibitors
D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D010436:Pepstatins; D000092502:Renin Inhibitors; C014195:Streptomyces pepsin inhibitor