Effects of des-aspartate-angiotensin I on the expression of angiotensin AT1 and AT2 receptors in ventricles of hypertrophic rat hearts

The effects of des-aspartate-angiotensin I (DAA-I) on the expression of angiotensin AT(1) and AT(2) receptor in hearts of aortic coarcted rats were studied. The protocols used included competitive reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and receptor-ligand binding assays. mRNA of the AT(1) and AT(2) receptors increased significantly after 4 days of aortic coarctation (7- and 4-folds of sham-operated, respectively). However, the protein of the AT(1) receptor was not altered, and only increase in protein of the AT(2) receptor was detected. There was an increase in [I-125]Sar(1)-Ile(8)-angiotensin II binding sites in the ventricular membranes of hypertrophic hearts, which was attributed to an upregulation of the AT(2) receptor. Treatment with i.p. DAA-I resulted in a significant reduction of cardiac hypertrophy, the maximum effect was achieved with a dose of 200 nmol/kg/day. The anti-cardiac hypertrophy effect appeared to be U-shape, and at a higher dose of 800 mol/kg/day, there was a loss of effect. DAA-I had no effect on the receptor protein in ventricles of hypertrophic hearts. However, DAA-I dose-dependently decreased the binding of [I-125] Sarl-Ile(8)-angiotensin II to ventricular membranes. The decrease was due to a likely desensitization by internalization of the AT(1) receptor, and this probably contributed to the loss of hypertrophic effects at 800 nmol/kg/day. Treatment of DAA-I also resulted in a remarkable increase in AT(2) receptor mRNA (24-fold increase over the sham-operated), which was not coupled to translation. The present findings provide new information regarding the relationship between cardiac hypertrophy and the angiotensin receptors, and the anti-cardiac hypertrophic actions of DAA-I via the AT, receptors. (C) 2003 Elsevier B.V. All rights reserved.