Comparison of angiotensin II type 1-receptor blockers to regress pressure overload-induced cardiac hypertrophy in mice

Abstract

Angiotensin II (AngII) type 1-receptor blockers (ARBs) have been effectively used not only in the treatment of hypertension but also in cardiac protection. However, whether and why there are differences in these effects still remain unclear. Here we compared the effects of five commonly used ARBs (Candesartan, Olmesartan, Losartan, Telmisartan and Valsartan) on pressure overload-induced cardiac hypertrophy in mice model. Pressure overload was produced by constriction of the transverse aorta (TAC) for 2 weeks, which induced a significant elevation of blood pressure; ARBs or saline was administered through a stomach tube; Cardiac hypertrophy was evaluated by transthoracic echocardiography, cardiac histology and specific gene expression analyses. Although all the five ARBs, which did not repress the elevation of left ventricular pressure after TAC, attenuated the development of cardiac hypertrophy in the wild-type mice, the degrees of regression by Candesartan, Olmesartan and Losartan tended to be larger than those by Telmisartan and Valsartan. Furthermore, in angiotensinogen-knockout mice lacking endogenous AngII, TAC-induced cardiac hypertrophy was regressed by Candesartan, Olmesartan and Losartan but not by Telmisartan and Valsartan administration. Our data suggest that Candesartan, Olmesartan and Losartan can effectively inhibit pressure overload-induced cardiac hypertrophy even in the absence of AngII, whereas Telmisartan and Valsartan could exert the inhibitory effects only in the presence of AngII.