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-2 alpha and PGD(2), 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 in the K-ATP(+) channel opener levcromakalim. 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 PGE(1). 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.