Effects of U-37883A, a vascular selective K(ATP)/+ channel antagonist, in the pulmonary and hindlimb circulation
The effects of the vascular selective nonsulfonylurea guanidine ATP- sensitive K+ (K(ATP)/+) channel-blocking agent U-37883A on vasodilator and vasoconstrictor responses were investigated in the pulmonary and hindlimb vascular beds of the cat. Under elevated tone conditions, both U-37883A and the sulfonylurea K(ATP)/+ antagonist, glibenclamide, attenuated pulmonary vasodilator responses to the K(ATP)/+ channel openers without altering responses to vasodilator agents that are reported to act by K(ATP)/+- independent mechanisms. However, under low resting-tone conditions, U-37883A enhanced pulmonary vasoconstrictor responses to the thromboxane mimic U- 46619 and to prostaglandin (PG) F(2α) and PGD2, whereas glibenclamide antagonized responses to U-46619 and the vasoconstrictor PG. In the hindlimb vascular bed, U-37883A and glibenclamide had no effects on responses to U- 46619 in doses that inhibited vasodilator responses to the K(ATP)/+ channel opener leveromakalim. U-37883A and glibenclamide had no significant effect on baseline tone in the pulmonary or hindlimb vascular beds, and neither U- 37883A nor glibenclamide altered pulmonary vasodilator responses to PGE1. The results of the present investigation show that U-37883A and glibenclamide, agents that are used in the study of vascular smooth muscle K(ATP)/+ channel mechanisms and attenuate vasodilator responses to the K(ATP)/+ channel openers, have pronounced effects on thromboxane/PG receptor-mediated vasoconstrictor responses in the pulmonary vascular bed of the cat.
DeWitt, BJ; Cheng, DY; McMahon, TJ; Marrone, JR; Champion, HC; Kadowitz, PJ
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