Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells

Abstract

The octapeptide [Ile5]angiotensin II (ANG II), which is the principal circulating hormone of the renin-angiotensin system, could modulate or mediate cardiac hypertrophy via indirect effects, through increases in total peripheral vascular resistance, or by direct effects on cardiac cells, which result in increased protein synthesis and cell growth. In this study we determined whether ANG II stimulated protein synthesis and cell growth in cultures of embryonic chick myocytes. After 3 h of exposure to ANG II, there were significant increases in total cellular protein at 120, 144, and 168 h and in the relative rate of protein synthesis at 120 and 144 h. There was a significant increase in the fractional rate of protein synthesis of 32.2% (0.0119 +/- 0.0008 h-1 for ANG II stimulated and 0.0090 +/- 0.0003 h-1 for control). The stimulatory effects of ANG II on protein synthesis and cell growth were inhibited by the ANG II antagonist [Sar1,Ile8]ANG II and the hexapeptide ANG II-(3-8). ANG II significantly increased total RNA levels in myocytes, at 12 h after exposure to the peptide. The stimulatory effect of ANG II (32%) on total cellular protein was slightly greater than that seen with norepinephrine (20%) in contrast to the greater stimulatory effect seen with phorbol 12,13-dibutyrate (47%). ANG II and [Sar1,Ile8]ANG II each stimulated increases in cytosolic-free Ca2+, whereas ANG II-(3-8) did not. Growth-related effects of changes in the chronotropic state of the myocytes were excluded, in that, ANG II-stimulated increases in protein synthesis and cellular protein were not inhibited by potassium chloride depolarization of the cells.(ABSTRACT TRUNCATED AT 250 WORDS)