Effects of losartan, an angiotensin II antagonist, on the development of cardiac hypertrophy due to volume overload.
To investigate the contribution of a cardiac renin-angiotensin system to cardiac hypertrophy due to volume overload, the effects of losartan, a non-peptide angiotensin (Ang) II type 1 (AT1) receptor antagonist on left ventricular hypertrophy (LVH) was studied. LVH was produced in male Wistar rats by volume overload secondary to aortic insufficiency (AI). Losartan (10 mg/kg/d) was orally administered for 2 weeks after surgery to both AI and sham-operated (control) rats. Two weeks after surgery, aortic pulse pressure and left ventricular (LV) weight were markedly increased in the AI rats as compared with the control group, whereas cardiac angiotensin converting enzyme (ACE) activity remained unchanged. The effects of the chronic administration of losartan an AT1 receptors were verified by the blockade of Ang II pressor response. Losartan treatment produced a significant reduction in LVH in AI rats without affecting the systolic blood pressure. In separate groups of rats, to elucidate the mechanisms of the attenuation of LVH by treatment with losartan, we determined plasma and LV immunoreactive Ang II content and plasma renin activity (PRA). LV Ang II content increased in AI rats, while plasma Ang II content, PRA and II concentration were increased by the treatment. There was a significant positive correlation between LV weight and LV Ang II content. These results suggest that cardiac Ang II, rather than circulating Ang II, plays an important role in the LVH due to volume overload via the AT1 receptor.
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000097:blood; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002306:Cardiac Volume / Q000502:physiology*; D006332:Cardiomegaly / Q000517:prevention & control*; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000494:pharmacology*
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D019808:Losartan