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Am J Physiol Heart Circ Physiol 266: H2443-H2451, 1994;
0363-6135/94 $5.00
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AJP - Heart and Circulatory Physiology, Vol 266, Issue 6 2443-H2451, Copyright © 1994 by American Physiological Society

ARTICLES

Hypertrophic growth of cultured neonatal rat heart cells mediated by type 1 angiotensin II receptor

S. Miyata and T. Haneda
First Department of Internal Medicine, Asahikawa Medical College, Hokkaido, Japan.

Primary cultures of neonatal cardiac myocytes were used to determine the identity of second messengers that are involved in angiotensin II (ANG II) receptor-mediated effects on cardiac hypertrophy and the type of ANG II receptor that is involved in ANG II-induced cell growth. Treatment of myocytes with ANG II significantly increased the protein-to-DNA and the RNA-to-DNA ratios. ANG II accelerated rates of protein synthesis by 24.9%. Intracellular free calcium was transiently increased after ANG II exposure. The activity of protein kinase C in particulate fractions was transiently increased after exposure to ANG II but returned to control level. The activity of protein kinase C in the cytosol was significantly decreased at all times after exposure to ANG II. After ANG II treatment, the content of c-Fos mRNA was increased. The stimulatory effects of ANG II on these parameters were inhibited by the type 1 angiotensin II receptor (AT1) antagonist, losartan. These studies demonstrate that ANG II-induced hypertrophic growth is, at least in part, mediated through AT1 receptors.


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