Effects of U-37883A, a vascular selective KATP+ channel antagonist, in the pulmonary and hindlimb circulation.

Published

Journal Article

The effects of the vascular selective nonsulfonylurea guanidine ATP-sensitive K+ (KATP+) 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 KATP+ antagonist, glibenclamide, attenuated pulmonary vasodilator responses to the KATP+ channel openers without altering responses to vasodilator agents that are reported to act by KATP(+)-independent mechanisms. However, under low resting-tone conditions, U-37883A enhanced pulmonary vasoconstrictor responses to the thromboxane mimic U-46619 and to prostaglandin (PG) F2 alpha 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 KATP+ 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 PGE1. The results of the present investigation show that U-37883A and glibenclamide, agents that are used in the study of vascular smooth muscle KATP+ channel mechanisms and attenuate vasodilator responses to the KATP+ channel openers, have pronounced effects on thromboxane/PG receptor-mediated vasoconstrictor responses in the pulmonary vascular bed of the cat.

Full Text

Duke Authors

Cited Authors

  • DeWitt, BJ; Cheng, DY; McMahon, TJ; Marrone, JR; Champion, HC; Kandowitz, PJ

Published Date

  • December 1996

Published In

Volume / Issue

  • 271 / 6 Pt 1

Start / End Page

  • L924 - L931

PubMed ID

  • 8997262

Pubmed Central ID

  • 8997262

International Standard Serial Number (ISSN)

  • 0002-9513

Digital Object Identifier (DOI)

  • 10.1152/ajplung.1996.271.6.L924

Language

  • eng

Conference Location

  • United States