Evidence for angiotensin II type 2 receptor-mediated cardiac myocyte enlargement during in vivo pressure overload

The pathophysiological roles of the angiotensin II type 2 receptor (AT(2)) in cardiac hypertrophy remain unclear. By the targeted deletion of mouse AT(2) we mere able to prevent the left ventricular hypertrophy resulting From pressure overload, while cardiac contractile functions remained normal. This implies that AT(2) is a mediator of cardiac hypertrophy in response to increased blood pressure. The effects of AT(2) deletion were independent of activation of embryonic genes for cardiac hypertrophy. However, p70(S6k), one of the key factors in cardiac hypertrophy, was markedly and specifically reduced in the ventricles of Agtr2(-)/Y mice. We propose that p70(S6k) plays a major role in AT(2)-mediated ventricular hypertrophy.