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-se nsitive K+ (K-ATP(+)) channel-blocking agent U-37883A on vasodilator a nd vasoconstrictor responses were investigated in the pulmonary and hi ndlimb vascular beds of the cat. Under elevated tone conditions, both U-37883A and the sulfonylurea K-ATP(+) antagonist, glibenclamide, atte nuated 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-to ne conditions, U-37883A enhanced pulmonary vasoconstrictor responses t o the thromboxane mimic U-46619 and to prostaglandin (PG) F-2 alpha an d PGD(2), whereas glibenclamide antagonized responses to U-46619 and t he vasoconstrictor PG. In the hindlimb vascular bed, U-37883A and glib enclamide had no effects on responses to U-46619 in doses that inhibit ed 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 r esults of the present investigation show that U-37883A and glibenclami de, 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 recepto r-mediated vasoconstrictor responses in the pulmonary vascular bed of the cat.