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(Hypertension. 1995;26:738.)
© 1995 American Heart Association, Inc.

Articles

Chronic Angiotensin-Converting Enzyme Inhibition and Endothelial Function of Rat Aorta

Guy Berkenboom; Dmitri Brékine; Philippe Unger; Katrina Grosfils; Michel Staroukine; Jeanine Fontaine

From the Department of Cardiology, Erasme Hospital, and Department of Pharmacology (K.G., J.F.), Institute of Pharmacy, Université Libre de Bruxelles (Belgium).

Correspondence to G. Berkenboom, MD, Cardiology Department, Erasme Hospital, Route de Lennik 808, 1070 Brussels, Belgium.

Abstract To determine whether chronic angiotensin-converting enzyme (ACE) inhibition produces functional changes in the aorta of normotensive rats, four groups of rats were studied in parallel for 6 weeks. Group 1 orally received ramipril 10 mg/kg per day for 6 weeks; group 2, ramipril 10 mg/kg per day for 4 weeks and then a cotreatment with ramipril and ß₂-kinin antagonist HOE140 500 µg/kg per day SC by injection for the remaining 2 weeks; group 3, hydralazine 100 mg/kg per day PO for 6 weeks; group 4 (control), subcutaneous injections of saline solution during the last 2 of 6 weeks. In aorta isolated from group 1 the relaxations induced by bradykinin, acetylcholine, and histamine were significantly potentiated compared with those of group 4. In group 3, despite a decrease in systolic blood pressure similar to that induced by ramipril treatment, the responses to these three endothelium-dependent vasodilators were not different from those of group 4. In group 2, bradykinin-induced relaxations were completely abolished whereas acetylcholine-induced and histamine-induced relaxations were similar to those of group 4. The inhibitory effect of the endothelium on serotonin-induced contractions was significantly increased in preparations of group 1 compared with those of groups 2 through 4. Indirect measurements of nitric oxide formation such as contractions evoked by N^G-monomethyl-L-arginine (L-NMMA) and aortic cGMP content were also significantly enhanced in preparations from group 1 compared with those of groups 2 and 4. Moreover, because the relaxations to nitroglycerin and nitroprusside were similar in groups 1, 2, and 4 an alteration of the guanylate cyclase activity by ramipril treatment is quite unlikely. Thus long-term treatment with ramipril potentiates the endothelium-dependent responses in the rat aorta by enhancing nitric oxide availability. This effect seems to involve an inhibition of bradykinin breakdown facilitating nitric oxide release via endothelial ß₂-receptors.

Key Words: angiotensin-converting enzyme inhibitors • bradykinin • endothelium • rat

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