Segmental differences in angiotensin receptor subtypes in interlobular artery of hydronephrotic rat kidneys.
Recent studies demonstrate that angiotensin II (ANG II)-induced vascular action is mediated preferentially by AT1 receptors. Although autoradiographic studies indicate the presence of AT2 receptors in large preglomerular vessels, functional roles for AT2 receptors in ANG II-induced renal vasoconstriction remain undetermined. We examined the effects of DuP-753 and PD-123319 on ANG II-induced vasoconstriction of interlobular arteries (ILA) in isolated perfused hydronephrotic rat kidneys to directly assess the AT1- and AT2-mediated action of ANG II on renal microvessels. Both DuP-753 (0.1-10 microM) and PD-123319 (0.1-10 microM) elicited dose-dependent vasodilation of ANG II-induced ILA constriction, with 86 +/- 4% and 36 +/- 4% inhibition by 10 microM DuP-753 and PD-123319, respectively. The reversal by DuP-753 of ANG II-induced ILA vasoconstriction was greater in small-caliber segments than in large-caliber segments. In contrast, the ability of PD-123319 (10 microM) to inhibit the vasoconstriction was augmented as the vessel diameter increased (slope = +0.46, correlation coefficient = +0.68; P < 0.01). Thus, although AT1 predominantly mediates the ANG II-induced ILA vasoconstriction, PD-123319-sensitive ANG II receptors (e.g., AT2 or AT1B) may also participate partly in the ILA vasoconstriction, particularly at large-caliber segments. In conclusion, distribution of ANG II receptor subtypes may differ depending on the size of the renal microvasculature.
Hayashi
K
K
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Suzuki
H
H
Saruta
T
T
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology; D006869:Hydronephrosis / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D010477:Perfusion; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan