[Sar1]angiotensin II receptor-mediated stimulation of protein synthesis in chick heart cells

Abstract

Cardiac hypertrophy is a process that occurs in response to various mechanical or hormonal stimuli. Stimulation of the renin-angiotensin system is involved in the process of cardiac hypertrophy through mechanisms related to increased peripheral vascular resistance and increased cardiac afterload. In this study we determined whether [Sar1]angiotensin II (ANG II) directly stimulated protein synthesis and cell growth in embryonic chick myocytes in cell culture. Eighteen-day-old embryonic chick myocytes in subconfluent cell culture, incubated in a chemically defined serum-free media, showed a significant increase in total protein content, 18.5, 26.2, and 22.2%, respectively, when exposed to [Sar1]ANG II (1 microM/day) for 5, 7, and 9 days, respectively. The increase in total protein resulted in part from an increase in the fractional protein synthesis rate of 21.7, 16.5, and 14.9% at 5, 7, and 9 days, respectively. Total DNA and RNA levels did not change significantly following a 4-day exposure to [Sar1]ANG II in subconfluent culture. The relative rate of protein synthesis, determined by pulse labeling for 3 h with [3H]phenylalanine, showed increases of 23.4, 22.9, and 17.8% over control after 4, 5, and 6 days of exposure to [Sar1]ANG II. The incorporation of [3H]phenylalanine was blocked by the specific ANG II-receptor antagonist [Sar1,Ile8]ANG II. The data demonstrate a receptor-mediated increase in the rate of protein synthesis in cultured chick myocytes in response to [Sar1]ANG II, with a resultant increase in total cellular protein. This angiotensin peptide appears to directly stimulate protein synthesis in cultured embryonic chick myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)