TP receptor - mediated vasoconstriction in microperfused afferent arterioles : roles of O 2 2 and NO CHRISTINE

and NO. Am J Physiol Renal Physiol 279: F302–F308, 2000.—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 2 in rabbit isolated, perfused renal afferent arteriole responses to the TxA2/prostaglandin H2 (TP) receptor agonist U-46,619. U-46,619 (10–10 M) dose-dependently reduced afferent arteriolar luminal diameter (ED50 5 7.5 6 5.0 nM), which was blocked by the TP receptor antagonist ifetroban (10 M). Tempol (10 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-nitro-Larginine methyl ester (L-NAME, 10 M) or L-NAME 1 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 2