TP receptor-mediated vasoconstriction in microperfused afferent arterioles: roles of O2 − and NO

Abstract

Thromboxane A2 (TxA2) preferentially constricts the renal afferent arteriole. Nitric oxide (NO) modulates vasoconstriction and is rapidly degraded by superoxide radical (O2 −). We investigated the roles of NO and O2 − in rabbit isolated, perfused renal afferent arteriole responses to the TxA2/prostaglandin H2 (TP) receptor agonist U-46,619. U-46,619 (10−10–10−6 M) dose-dependently reduced afferent arteriolar luminal diameter (ED50 = 7.5 ± 5.0 nM), which was blocked by the TP receptor antagonist ifetroban (10−6 M). Tempol (10−3 M) pretreatment, which prevented paraquat-induced vasoconstriction in afferent arterioles, blocked the vasoconstrictor responses to U-46,619. To test whether U-46,619 stimulates NO and whether tempol prevents U-46,619-induced vasoconstriction by enhancing the biological activity of NO, we examined the luminal diameter response to U-46,619 in arterioles pretreated with N w-nitro-l-arginine methyl ester (l-NAME, 10−4 M) or l-NAME + tempol. During l-NAME, the sensitivity and maximal responses of the afferent arteriole to U-46,619 were significantly ( P < 0.05) enhanced. Moreover, l-NAME restored a vasoconstrictor response to U-46,619 in vessels pretreated with tempol. In conclusion, in isolated perfused renal afferent arterioles TP receptor activation stimulates NO production, which buffers the vasoconstriction, and stimulates O2 −production, which mediates the vasoconstriction, in part, through interaction with NO.