ALTERATIONS OF ANGIOTENSIN-II RECEPTOR CONTENTS IN HYPERTROPHIED HEARTS

Tsukuba hypertensive mice, which carry the human genes for renin and angiotensinogen, show cardiac hypertrophy as well as hypertension due to activation of the renin-angiotensin system (RAS). Here, we compared the cardiac angiotensin II (Ang II) receptor contents in these and normotensive control mice by means of Ligand binding studies and competitive reverse transcription-polymerase chain reaction analyses. The content 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) levels in the hypertensive mice than that in control mice. Almost identical levels of the Ang II receptor type 2 (AT(2)) expression were identified 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 results suggest that AT(1) in the heart is upregulated in response to Ang II-induced hypertrophic change and that, in particular, the upregulation of AT(1) in particular contributes to the development and/or maintenance of cardiac hypertrophy in conjunction with the increase in Ang II production, because ATI is responsible for cardiac hypertrophy related to the RAS. (C) 1995 Academic Press, Inc.