ALTERATIONS OF ANGIOTENSIN-II RECEPTOR CONTENTS IN HYPERTROPHIED HEARTS

Tsukuba hypertensive mice, which carry the human genes for renin and a ngiotensinogen, show cardiac hypertrophy as well as hypertension due t o activation of the renin-angiotensin system (RAS). Here, we compared the cardiac angiotensin II (Ang II) receptor contents in these and nor motensive control mice by means of Ligand binding studies and competit ive reverse transcription-polymerase chain reaction analyses. The cont ent of the Ang II receptor type 1 (AT(1)) was significantly higher at both the protein (2.5-fold; p < 0.01) and mRNA (1.4-fold; p < 0.05) le vels in the hypertensive mice than that in control mice. Almost identi cal levels of the Ang II receptor type 2 (AT(2)) expression were ident ified at the mRNA levels in the two types of mice, although the levels were less than 20% of those of AT(1) mRNA in control mice. These resu lts suggest that AT(1) in the heart is upregulated in response to Ang II-induced hypertrophic change and that, in particular, the upregulati on of AT(1) in particular contributes to the development and/or mainte nance of cardiac hypertrophy in conjunction with the increase in Ang I I production, because ATI is responsible for cardiac hypertrophy relat ed to the RAS. (C) 1995 Academic Press, Inc.