NG-Nitro-l-Arginine Methyl Ester–Induced Hypertension and Natriuretic Peptide Gene Expression: Inhibition by Angiotensin II Type 1 Receptor Antagonism

Abstract

This study examined the role of angiotensin II in the increase of blood pressure, activation of cardiac natriuretic peptide gene expression, left ventricular hypertrophy, and vascular changes in nitric oxide–deficient hypertension. NG-nitro-l-arginine methyl ester (l-NAME, 20 mg/kg/d), angiotensin II type 1 receptor (AT1) antagonist losartan (20 mg/kg/d), or their combination were administered orally for 8 weeks in Wistar rats. l-NAME elevated systolic blood pressure, which reached its maximum within 4 weeks (200 ± 4 mm Hg). Despite hypertension, l-NAME administration for 8 weeks did not induce left ventricular hypertrophy. Losartan treatment significantly decreased the development of hypertension induced by l-NAME and decreased left ventricular hypertrophy in untreated rats. In contrast, losartan did not prevent the hypertrophic remodeling of the mesenteric resistance arteries induced by l-NAME. l-NAME treatment increased ventricular atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) mRNA levels and immunoreactive BNP levels significantly. Losartan therapy decreased the l-NAME-induced ventricular ANP gene expression by 69% (p