Differential effects of u-37883a, a vascular selective k+atp
channel antagonist, in the pulmonary and hindlimb vascular bed of the
cat.
Dewitt, Bracken J., David Y. Cheng, Timothy J. McMahon, James R.
Marrone, Hunter C. Champion, and Philip J. Kadowitz.
Department of Pharmacology, Tulane University School of Medicine,
New Orleans, Louisiana 70112
APStracts 3:0128L, 1996.
The effects of the vascular selective nonsulfonylurea guanidine K+ATP
channel-blocking agent, U-37883A, on vasodilator and vasoconstrictor
responses were investigated in the pulmonary and hindlimb vascular
bed of the cat. Under elevated-tone conditions, both U-37883A and the
sulfonylurea K+ATP antagonist, glybenclamide, 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, U46619, and to PGF2[alpha] and PGD2, whereas
glybenclamide antagonized responses to U46619 and the vasoconstrictor
prostaglandins. In the hindlimb vascular bed, U-37883A and
glybenclamide had no effects on responses to U46619 in doses that
inhibited vasodilator responses to the K+ATP channel opener,
levcromakalim. U-37883A and glybenclamide had no significant effect
on baseline tone in the pulmonary or hindlimb vascular bed, and
neither U-37883A nor glybenclamide altered pulmonary vasodilator
responses to PGE1. The results of the present investigation show that
U-37883A and glybenclamide, agents which 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/prostaglandin receptor-mediated
vasoconstrictor responses in the pulmonary vascular bed of the cat.
Received 13 November 1995; accepted in final form 24 July 1996.
APS Manuscript Number L325-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996