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2015 ; 65
(3
): 226-32
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AT2 receptor activities and pathophysiological implications
#MMPMID25636068
Matavelli LC
; Siragy HM
J Cardiovasc Pharmacol
2015[Mar]; 65
(3
): 226-32
PMID25636068
show ga
Although angiotensin II subtype-2 receptor (AT2R) was discovered over 2 decades
ago, its contribution to physiology and pathophysiology is not fully elucidated.
Current knowledge suggests that under normal physiologic conditions, AT2R
counterbalances the effects of angiotensin II subtype-1 receptor (AT1R). A major
obstacle for AT2R investigations was the lack of specific agonists. Most of the
earlier AT2R studies were performed using the peptidic agonist, CG42112A, or the
nonpeptidic antagonist PD123319. CGP42112A is nonspecific for AT2R and in higher
concentrations can bind to AT1R. Recently, the development of specific
nonpeptidic AT2R agonists boosted the efforts in identifying the therapeutic
potentials for AT2R stimulation. Unlike AT1R, AT2R is involved in vasodilation by
the release of bradykinin and nitric oxide, anti-inflammation, and healing from
injury. Interestingly, the vasodilatory effects of AT2R stimulation were not
associated with significant reduction in blood pressure. In the kidney, AT2R
stimulation produced natriuresis, increased renal blood flow, and reduced tissue
inflammation. In animal studies, enhanced AT2R function led to reduction of
cardiac inflammation and fibrosis, and reduced the size of the infarcted area.
Similarly, AT2R stimulation demonstrated protective effects in vasculature and
brain.
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