Effects of losartan on angiotensin receptors in the hypertrophic rat heart

The effects of losartan on angiotensin receptors in hypertrophic rat hearts were studied. The study was prompted by inconsistent findings of either an increase or decrease in the mRNA of the AT, receptor in the hearts of cardiac hypertrophic rats treated with losartan, and a paucity of information on the effects of losartan on functional angiotensin receptors in the heart. Losartan, administered i.p. to aortic coarcted rats, dose-dependently attenuated the cardiac hypertrophy. Significant effect was observed with a dose of 2.72 mu mol/kg/day for four days. Hypertrophy was accompanied by an increase in [I-125]-Sar(1) -Ile(8)-angiotensin II binding sites (due mainly to an increase in AT(2) binding) and AT(2) receptor protein in cardiac ventricles of aortic coarcted rats. Treatment with effective anti-hypertrophic doses of losartan dose-dependently downregulated the [I-125]-Sar(1)-Ile(8)-angiotensin II binding sites, constitutive AT(1) receptor protein, and the over expressed AT(2) receptor protein. It was suggested that the anticardiac hypertrophic action of losartan resulted from its ability to suppress the expression of both the basal and enhanced cardiac angiotensin receptors. This raises the question as to whether such drastic action could form the therapeutic basis for the use of losartan in cardiac pathologies. (c) 2006 Elsevier B.V. All rights reserved.