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 (AT₁) 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 (AT₂) expression were identified at the mRNA levels in the two types of mice, although the levels were less than 20% of those of AT₁ mRNA in control mice. These results suggest that AT₁ in the heart is upregulated in response to Ang II-induced hypertrophic change and that, in particular, the upregulation of AT₁ in particular contributes to the development and/or maintenance of cardiac hypertrophy in conjunction with the increase in Ang II production, because AT₁ is responsible for cardiac hypertrophy related to the RAS.