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 Il-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 μM) and PD-123319 (0.1-10 μM) elicited dose-dependent vasodilation of ANG II-induced ILA constriction, with 86 ± 4% and 36 ± 4% inhibition by 10 μM 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 μM) 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 AT_1B) may also participate partly in the ILA vasoconstriction, particularly at large-caliber segments. In conclusion, distribution of ANGII receptor subtypes may differ depending on the size of the renal microvasculature.