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(Hypertension. 1999;33:329-334.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Effect of ACE Inhibitor on DOCA-Salt– and Aortic Coarctation–Induced Hypertension in Mice

Do Kinin B₂ Receptors Play a Role?

Nour-Eddine Rhaleb; Hongmei Peng; Marcos E. Alfie; Edward G. Shesely; Oscar A. Carretero

From the Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich.

Correspondence to Nour-Eddine Rhaleb, PhD, Room 7015 Education & Research Building, Henry Ford Hospital, Hypertension and Vascular Research Division, 2799 West Grand Blvd, Detroit, MI 48202-2689. E-mail nrhaleb1{at}hfhs.org

Abstract—Kinins have been shown to play an important role in the cardioprotective effect of ACE inhibitors (ACEi) during heart failure and ischemia-reperfusion. However, it is controversial as to whether kinins oppose the hypertensinogenic effect of deoxycorticosterone acetate plus salt (DOCA-salt) or aortic coarctation and whether they mediate both chronic antihypertensive and cardiac antihypertrophic effects of ACEi in hypertension. Using normal 129/SvEvTac mice and mice lacking the bradykinin B₂ receptor gene (B₂-KO), we investigated whether (1) the hypertensinogenic effect of DOCA-salt or aortic coarctation is enhanced in B₂-KO mice and (2) the chronic antihypertensive and antihypertrophic effects of an ACEi (ramipril, 4 mg · kg^-1 · d^-1) are mediated by B₂ receptors in aortic coarctation (6 weeks)– and DOCA-salt (4 weeks)–induced hypertension. Before surgery, there was no difference between 129/SvEvTac and B₂-KO mice in terms of blood pressure and heart weight, suggesting that kinins are not essential to maintaining normal blood pressure. DOCA-salt (volume expansion) or aortic coarctation (renin-dependent) induced similar hypertension and left ventricular hypertrophy (LVH) in 129/SvEvTac and B₂-KO mice, suggesting that kinins do not play an essential role in the development of DOCA-salt– or aortic coarctation–induced hypertension. We found that B₂ receptors mediate only the early (1 week) but not the late phase (4 weeks) of the chronic hypotensive effect of ACEi in DOCA-salt hypertension. On the other hand, chronic ACE inhibition prevented the development of hypertension and LVH in both 129/SvEvTac and B₂-KO mice given DOCA-salt or subjected to aortic coarctation, suggesting that kinins do not participate in the chronic antihypertensive and antihypertrophic effects of ACEi in these 2 models of hypertension. Thus, in mice, kinins acting via B₂ receptors do not participate in (1) maintenance of normal basal blood pressure, (2) establishment and maintenance of hypertension induced by DOCA-salt or aortic coarctation, and (3) chronic antihypertensive and cardiac antihypertrophic effects of ACEi in DOCA-salt and aortic coarctation hypertension.

Key Words: receptors, bradykinin • angiotensin-converting enzyme inhibitors • deoxycorticosterone • coarctation, aortic • blood pressure • gene regulation

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