Effect of ACE inhibitor on DOCA-salt- and aortic coarctation-induced hypertension in mice - Do kinin B-2 receptors play a role?

Kiplins have been shown to play an important role in the cardioprotective e ffect of ACE inhibitors (ACEi) during heart failure and ischemia-reperfusio n. However, it is controversial as to whether kinins oppose the hypertensin ogenic effect of deoxycorticosterone acetate plus salt (DOCA-salt) or aorti c coarctation and whether they mediate both chronic antihypertensive and ca rdiac antihypertrophic effects of ACEi in hypertension Using normal 129/SvE vTac mice and mice lacking the bradykinin B-2 receptor gene (B-2-KO), we in vestigated whether (1) the hypertensinogenic effect of DOCA-salt or aortic coarctation is enhanced in B-2-KO mice and (2) the chronic antihypertensive and antihypertrophic effects of an ACEi (ramipril, 4 mg . kg(-1) . d(-1)) are mediated by B-2 receptors in aortic coarctation (6 weeks)- and DOCA-sal t (4 weeks)-induced hypertension. Before surgery, there was no difference b etween 129/SvEvTac and B-2-KO mice in terms of blood pressure and heart wei ght, suggesting that kinins are not essential to maintaining normal blood p ressure. DOCA-salt (volume expansion) or aortic coarctation (renin-dependen t) induced similar hypertension and left ventricular hypertrophy (LVH) in 1 29/SvEvTac and B-2-KO mice, suggesting that kinins do not play an essential role in the development of DOCA-salt- or aortic coarctation-induced hypert ension. We found that B-2 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 B-2-KO mice gi ven DOCA-salt or subjected to aortic coarctation, suggesting that kinins do not participate in the chronic antihypertensive and antihypertrophic effec ts of ACEi in these 2 models of hypertension. Thus, in mice, kinins acting via B-2 receptors do not participate in (1) maintenance of normal basal blo od pressure, (2) establishment and maintenance of hypertension induced by D OCA-salt or aortic coarctation, and (3) chronic antihypertensive and cardia c antihypertrophic effects of ACEi in DOCA-salt and aortic coarctation hype rtension.