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

Bruna Gigante, Ornella Piras, Paola De Paolis, Antonio Porcellini, Armando Natale, Massimo Volpe

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. 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. Methods. 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. Results. Los reduced BP significantly in both intact (P <0.001) and NX (P <0.05) rats, while PD increased BP in intact and NX rats (both P <0.001). In the Los + PD group BP levels were significantly higher (P <0.001 vs Los and Los + vehicle, P = ns vs pretreatment), while vehicle infusion did not modify the BP response to Los. Conclusion. 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.

Original languageEnglish
Pages (from-to)2039-2043
Number of pages5
JournalJournal of Hypertension
Volume16
Issue number12 SUPPL.
DOIs
Publication statusPublished - 1998

Keywords

  • Angiotensin II receptors
  • Blood pressure
  • Losartan
  • PD123319

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

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