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. N(G)-nitro->L-arginine methyl ester (>L-NAME, 20 mg/kg/d), angiotensin II type 1 receptor (AT ) 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 < 0.05) and also reduced ventricular BNP mRNA levels so that it did not differ from control. Losartan treatment alone decreased ventricular immunoreactive ANP and BNP levels by 30% (p < 0.05). These results show that ventricular ANP and BNP gene expression are dissociated from the increased ventricular mass in nitric oxide deficiency-induced hypertension. Results suggest that >l-NAME-induced hypertension and the associated activation of ventricular ANP and BNP gene expression are, at least in part, mediated by angiotensin II, whereas the resistance vessel hypertrophy following nitric oxide synthase inhibition is angiotensin II independent.

AT 1 Receptor Blockade Improves Vasorelaxation in Experimental Renal Failure

“…34 It is of note that in experimental NO-deficient hypertension, AT 1 receptor blockade reduced blood pressure and cardiac load, but the mesenteric resistance vessels still showed an inward hypertrophic response. 17 The present results show that the effect of renal failure on resistance vessel structure and the correction of these changes by losartan can be dissociated from the level of blood pressure.…”

“…18 For endothelium-independent relaxation, the endothelium was removed by perfusing air through the lumen. Morphology of small arteries was examined with a pressure myograph (Living Systems Instrumentation Inc), as previously reported, 17 and the development of myogenic tone was inhibited by Ca 2ϩ -free solution containing 30 mmol/L EDTA. 19 …”

“…Blood and tissue samples were taken and processed as previously. 8,10,17 Remaining 8 NTX and 8 Sham rats were followed for a further 12 weeks until the age of 32 weeks, whereafter blood and tissue samples from these animals were taken. The experimental design was approved by the Animal Experimentation Committee of the University of Tampere, and the Provincial Government of Western Finland, Department of Social Affairs and Health, Finland.…”

Distinct modulation of angiotensin II-induced early left ventricular hypertrophic gene programming by dietary fat type

“…Moreover, we observed that Ang II infusion markedly downregulated iNOS mRNA levels in fatty acidsupplemented groups compared with the standard diet group. As nitric oxide attenuates ventricular natriuretic peptide expression (28), Ang II-induced inhibition of nitric oxide synthesis may contribute to the upregulation of ANP and BNP gene expression in the rat heart.…”

Increased calcium intake reduces plasma cholesterol and improves vasorelaxation in experimental renal failure

“…Morphology of small arteries was examined with a pressure myograph (Living Systems Instrumentation; Burlington, VT) as previously reported, and the development of myogenic tone was inhibited by Ca 2ϩ -free solution containing 30 mmol/l EDTA (30). Three 5-m aortic cross sections from the 18 rats that were followed for another 8 wk were stained with von Kossa stain and processed for light microscopic evaluation.…”