Role of the angiotensin II AT2-subtype receptors in the blood pressure-lowering effect of losartan in salt-restricted rats

Publisher Website
Google Scholar
Abstract
The aim of this study was to evaluate the potential role of the angiotensin II (Ang II) AT2 receptors (AT2) in the control of blood pressure (BP) in the rat and the effects of AT2 receptors on BP during AT1 receptor (AT1) antagonism. The study was performed in 52 Sprague–Dawley rats, which were preliminarily salt-restricted (SR) to enhance circulating and tissue renin–angiotensin system activity. To explore whether AT2 plays a role in BP regulation, the BP effects of the selective AT2 and AT1 receptor antagonists PD123319 (PD) (50 μg/kg/min) and losartan (Los) (10 mg/kg/day), were studied. Seven rats were used as a control group. To define whether AT2 plays a role in the BP response observed during AT1 antagonism, 17 Los treated rats were divided into two groups: seven were treated with both antagonists (Los + PD) and 10 rats received Los + vehicle. The effects of both drugs were also studied in bilaterally nephrectomized rats (NX). All treatments were maintained for 1 week. Los reduced BP significantly in both intact (P P The results show that in salt-restricted rats AT2 blockade offsets the BP-lowering effect of losartan and suggest that AT2 receptors contribute to the hypotensive effects of losartan. Thus, AT1 receptor antagonists such as losartan, which are becoming widely used in the clinical treatment of hypertension, may reduce BP not only by blockade of AT1 receptors, but also through the stimulation of AT2 receptors by the excess of angiotensin II.