Effects of U-37883A, a vascular selective KATP+ channel antagonist, in the pulmonary and hindlimb circulation
DeWitt, B.J.; Cheng, D.Y.; McMahon, T.J.; Marrone, J.R.; Champion, H.C.; Kandowitz, P.J.
American Journal of Physiology 271(6 Pt 1): L924-L931
1996
ISSN/ISBN: 0002-9513 PMID: 8997262 Document Number: 461020
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-37883 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-2alpha 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 to 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.