title: Effects of des-aspartate-angiotensin I on the expression of angiotensin AT1 and AT2 receptors in ventricles of hypertrophic rat hearts.
abstract: The effects of des-aspartate-angiotensin I (DAA-I) on the expression of angiotensin AT1 and AT2 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 AT1 and AT2 receptors increased significantly after 4 days of aortic coarctation (7- and 4-folds of sham-operated, respectively). However, the protein of the AT1 receptor was not altered, and only increase in protein of the AT2 receptor was detected. There was an increase in [125I]Sar1-Ile8-angiotensin II binding sites in the ventricular membranes of hypertrophic hearts, which was attributed to an upregulation of the AT2 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 [125I]Sar1-Ile8-angiotensin II to ventricular membranes. The decrease was due to a likely desensitization by internalization of the AT1 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 AT2 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 AT1 receptors.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National University of Singapore, 117597.
authors.forename: W S
authors.initials: WS
authors.lastname: Chen
authors.forename: M K
authors.initials: MK
authors.lastname: Sim
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology / Q000502:physiology; D000805:Angiotensin III / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001017:Aortic Coarctation / Q000473:pathology; D002312:Cardiomyopathy, Hypertrophic / Q000378:metabolism* / Q000473:pathology; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000805:Angiotensin III; D000803:Angiotensin I