Article date: July 2004
By: Xiao C Li, Robert E Widdop in Volume 142, Issue 5, pages 821-830
In the present study, we investigated the role of the angiotensin II type 2 receptor (AT2) receptor in the regulation of regional haemodynamics in spontaneously hypertensive rats (SHR). We tested the hypothesis that AT2 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 AT1 receptor antagonist, candesartan (5 or 10 μg kg−1 i.v.) alone, the AT2 receptor agonist, CGP42112 (1 μg kg−1 min−1) alone and candesartan plus CGP42112.
Low‐dose candesartan (5 μg 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 AT2 receptor antagonist, PD123319 (50 μg 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 AT1 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, AT2 receptors tonically modulate vascular tone and that direct AT2 receptor‐mediated vasodilatation was unmasked by AT1 receptor blockade.
In the present study, we investigated the role of the angiotensin II type 2 receptor (AT2) receptor in the regulation of regional haemodynamics in spontaneously hypertensive rats (SHR). We tested the hypothesis that AT2 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 AT1 receptor antagonist, candesartan (5 or 10 μg kg−1 i.v.) alone, the AT2 receptor agonist, CGP42112 (1 μg kg−1 min−1) alone and candesartan plus CGP42112.
Low‐dose candesartan (5 μg 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 AT2 receptor antagonist, PD123319 (50 μg 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 AT1 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, AT2 receptors tonically modulate vascular tone and that direct AT2 receptor‐mediated vasodilatation was unmasked by AT1 receptor blockade.
British Journal of Pharmacology (2004) 142, 821–830. doi:10.1038/sj.bjp.0705838
DOI: 10.1038/sj.bjp.0705838
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