Angiotensin II–Induced Growth Responses in Isolated Adult Rat Hearts

Abstract Cardiac myocyte hypertrophy often occurs in response to both hemodynamic and neurohumoral factors. To study whether activation of the renin-angiotensin system by itself may induce a cardiac growth response, the acute effects of angiotensin II on cardiac protein synthesis were studied in isolated rat hearts. New protein synthesis in isolated buffer-perfused adult rat hearts was measured by incorporation of 3 Hphenylalanine into cardiac proteins during a 3-hour perfusion protocol. Angiotensin II (1×10 −8 mol/L), administered alone or in combination with the α 1 -blocker prazosin (1×10 −7 mol/L), stimulated protein synthesis in both ventricles. The rate of 3 Hphenylalanine incorporation into cardiac proteins was 3.9-fold ( P 10 −9 mol/L caused a significant induction of c- fos in adult and neonatal cardiac myocytes. In conclusion, angiotensin II acutely stimulates protein synthesis in cultured adult isolated perfused rat hearts. Angiotensin II–activated signal transduction appears to involve AT 1 receptors and activation of PKC. However, further downstream signaling mechanisms remain elusive, since angiotensin II may stimulate protein synthesis in the adult intact heart without preceding c- fos and c- jun proto-oncogene induction.