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

Abstract

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 were 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.

Can Angiotensin II Type 2 Receptors Have Deleterious Effects in Cardiovascular Disease?

“…This study and several others that suggest either prohypertrophic or antihypertrophic effects of AT 2 are summarized in the Table. 7,[25][26][27][28][29][30] The fact that growth-promoting effects of AT 2 were not observed in earlier in vitro studies is not surprising, because AT 2 disappears rapidly in ordinary cell culture conditions. 10 However, the in vivo experiments shown in the Table appear to show that AT 2 both suppresses and promotes vascular cell growth, hypertrophy, and fibrosis, and these conflicting results are more difficult to explain.…”

“…10 However, the in vivo experiments shown in the Table appear to show that AT 2 both suppresses and promotes vascular cell growth, hypertrophy, and fibrosis, and these conflicting results are more difficult to explain. One possible explanation, as suggested by Inagami and Senbonmatsu, 10 lies in the fact that the strain of AT 2 -knockout mice used by Akishita et al 28,29 differed from that used by Senbonmatsu et al 26 In addition, the various studies examined cardiovascular responses under different conditions. Clearly, ligands, receptors, and transducers often play different roles depending on the particular environment and conditions and are not intrinsically "good" or "bad."…”

Vascular Endothelial Growth Factor Blockade Promotes the Transition From Compensatory Cardiac Hypertrophy to Failure in Response to Pressure Overload

“…1,2 However, after sustained external load, hearts can evolve to a state of decompensated hypertrophy resulting in cardiac dilation and loss of contractile function. Whereas it is known that overload-induced cardiac hypertrophy involves the participation of angiotensin II, 3 endothelin-1, 4 and fibroblast growth factor-2, 5 the molecular mechanisms responsible for the transition from compensated to decompensated hypertrophy are poorly defined.…”

Angiotensin II Type 2 Receptor–Mediated Gene Expression Profiling in Human Coronary Artery Endothelial Cells

“…These conclusions have been derived primarily using transgenic and knockout mice. [1][2][3][4][5][6][7] Despite these inconsistent findings, [1][2][3][4][5][6][7] it is generally accepted that the AT 2 receptor has a beneficial function in the cardiovascular system. Strong evidence for this conclusion has recently been provided by our studies.…”