TP receptor-mediated vasoconstriction in microperfused afferent arterioles: roles of O(2)(-) and NO.
Thromboxane A(2) (TxA(2)) preferentially constricts the renal afferent arteriole. Nitric oxide (NO) modulates vasoconstriction and is rapidly degraded by superoxide radical (O(2)(-)). We investigated the roles of NO and O(2)(-) in rabbit isolated, perfused renal afferent arteriole responses to the TxA(2)/prostaglandin H(2) (TP) receptor agonist U-46,619. U-46,619 (10(-10)-10(-6) M) dose-dependently reduced afferent arteriolar luminal diameter (ED(50) = 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 O(2)(-) production, which mediates the vasoconstriction, in part, through interaction with NO.
Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC, USA.
C G
CG
Schnackenberg
W J
WJ
Welch
C S
CS
Wilcox
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D010477:Perfusion; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000502:physiology*; D012079:Renal Circulation / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; D013481:Superoxides; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019331:NG-Nitroarginine Methyl Ester