Effects of U-37883A, a vascular selective KATP+ channel antagonist, in the pulmonary and hindlimb circulation.
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.
DeWitt
B J
BJ
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Cheng
D Y
DY
McMahon
T J
TJ
Marrone
J R
JR
Champion
H C
HC
Kandowitz
P J
PJ
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D002415:Cats; D005121:Extremities / Q000098:blood supply*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D011652:Pulmonary Circulation / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D009025:Morpholines; D026902:Potassium Channel Blockers; C082658:U 37883A; D000218:Adamantane; D005905:Glyburide