AT2 receptor‐mediated vasodilatation is unmasked by AT1 receptor blockade in conscious SHR
- 1 July 2004
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 142 (5), 821-830
- https://doi.org/10.1038/sj.bjp.0705838
Abstract
In the present study, we investigated the role of the angiotensin II type 2 receptor (AT(2)) receptor in the regulation of regional haemodynamics in spontaneously hypertensive rats (SHR). We tested the hypothesis that AT(2) receptor activation directly causes vasodilatation. Mean arterial pressure (MAP), renal, mesenteric and hindquarters flows and conductances were measured in various groups of conscious rats that received the following drug combinations on separate days: the AT(1) receptor antagonist, candesartan (5 or 10 microg kg(-1) i.v.) alone, the AT(2) receptor agonist, CGP42112 (1 microg kg(-1) min(-1)) alone and candesartan plus CGP42112. Low-dose candesartan (5 microg kg(-1)) caused renal vasodilatation, while CGP 42112 alone caused minimal haemodynamic effects. In the presence of candesartan, CGP42112 caused a marked depressor effect together with generalised vasodilatation that was abolished by the coinfusion of the AT(2) receptor antagonist, PD123319 (50 microg kg(-1) min(-1)), with the candesartan and CGP42112 combination. PD123319, given alone, increased MAP and reduced renal and mesenteric conductances. We also confirmed that the enhanced vasodilatation evoked by candesartan plus CGP42112 was not due to additional AT(1) receptor blockade, since angiotensin II-mediated vasoconstriction was inhibited by a similar magnitude in the combination treatment compared with candesartan alone. Analogous experiments in Wistar-Kyoto rats did not demonstrate significantly enhanced effects due to candesartan plus CGP42112. Collectively, these data suggest that, in SHR, AT(2) receptors tonically modulate vascular tone and that direct AT(2) receptor-mediated vasodilatation was unmasked by AT(1) receptor blockade.Keywords
This publication has 34 references indexed in Scilit:
- Angiotensin AT2 receptors: cardiovascular hope or hype?British Journal of Pharmacology, 2003
- Angiotensin Type 2 Receptor-Mediated Hypotension in Angiotensin Type-1 Receptor-Blocked RatsHypertension, 2001
- Angiotensin II Relaxes Microvessels Via the AT 2 Receptor and Ca 2+ -Activated K + (BK Ca ) ChannelsHypertension, 2001
- Activation of AT 2 Receptors by Endogenous Angiotensin II Is Involved in Flow-Induced Dilation in Rat Resistance ArteriesHypertension, 1999
- Modulation of AT1 receptor‐mediated contraction of rat uterine artery by AT2 receptorsBritish Journal of Pharmacology, 1998
- Opposing Actions of Angiotensin II on Microvascular Growth and Arterial Blood PressureHypertension, 1996
- Regional Hemodynamic Effects of the AT 1 Receptor Antagonist CV-11974 in Conscious Renal Hypertensive RatsHypertension, 1995
- Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor gene in miceNature, 1995
- Repeated measurements and multiple comparisons in cardiovascular researchCardiovascular Research, 1994
- Changes in expression of angiotensin receptor subtypes in the rat aorta during developmentBiochemical and Biophysical Research Communications, 1991