Function of angiotensin II type 2 receptor in the postglomerular efferent arteriole.
The balance of vasucular tone between afferent (Af-Art) and efferent arterioles (Ef-Art) is a critical determinant of the glomerular hemodynamics. We recently reported that selective activation of angiotensin II type 2 receptor (AT-2R) causes dilation in the Af-Art. However, the functional role of AT-2R in the Ef-Art has not been defined. In the present study, we microperfused rabbit Ef-Art in vitro, and examined the effect of angiotensin II (Ang II; 10(-11) to 10(-8) M) on the luminal diameter in the presence or absence of an AT-2R antagonist PD123319 (PD; 10(-7) M). Angiotensin II caused dose-dependent constriction in Ef-Arts, with a significant constriction occurring at 10(-11) M; at 10(-10) M the diameter decreased by 28 +/- 4% (N = 6). Pretreatment with PD significantly (P < 0.0125) augmented vasoconstrictor action of Ang II; at 10(-10) M the diameter decreased by 44 +/- 4% (N = 6). We then examined whether blockade of Ang II type 1 receptor (AT-1R) uncovers vasodilator action of Ang II mediated by AT-2R. Efferent arterioles were preconstricted by about 40% with norepinephrine and AT-1R was blocked with its selective antagonist CV11974 (CV; 10(-8) M). Angiotensin II added to preconstricted and CV-pretreated Ef-Arts caused a dose-dependent dilation; at 10(-8) M diameter increased by 28 +/- 3% (N = 5). The dilation was completely abolished by simultaneous pretreatment with PD (N = 4). Our results demonstrate that in the Ef-Art selective activation of AT-2R causes vasodilation, which opposes the vasoconstrictor action of Ang II.
Endo
Y
Y
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Arima
S
S
Yaoita
H
H
Omata
K
K
Tsunoda
K
K
Takeuchi
K
K
Abe
K
K
Ito
S
S
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; C081643:candesartan; D009638:Norepinephrine