Dk. Alan et al., DIFFERENTIAL-EFFECTS OF GLIBENCLAMIDE ON RESPONSES TO THROMBOXANE A2 MIMIC, U46619, IN THE PULMONARY AND HINDQUARTERS VASCULAR BEDS OF THE CAT, European journal of pharmacology, 340(2-3), 1997, pp. 187-193
The inhibitory effects of the oral sulfonylurea, glibenclamide, on vas
oconstrictor responses to the thromboxane A(2) mimic, U46619, were inv
estigated in the pulmonary and hindquarters vascular beds of the cat u
nder constant flow conditions. When lobar arterial tone was at resting
conditions (14 +/- 2 mm Hg), intralobar injections of U46619, prostag
landin F-2 alpha prostaglandin D-2, angiotensin II, norepinephrine, an
d BAY K 8644 caused dose-related increases in lobar arterial pressure
without altering left atrial pressure. Following an intralobar infusio
n of glibenclamide (5 mg/kg), vasoconstrictor responses to U46619, pro
staglandin F-2 alpha and prostaglandin D-2 were significantly reduced,
whereas vasoconstrictor responses to norepinephrine and angiotensin I
l were not altered and responses to BAY K 8644 were significantly enha
nced. When tone in the pulmonary vascular bed was raised to a high ste
ady level (36 +/- 3 mm Hg), glibenclamide in a dose of 5 mg/kg i.a. ma
rkedly attenuated responses to injections of U46619 and reduced the va
sodilator responses to the K+-ATP channel opener, levcromakalim, where
as responses to acetylcholine and S-nitroso-N-acetylpenicillamine (SNA
P), a nitric oxide donor, were not changed. In the hindquarters vascul
ar bed of the cat, administration of glibenclamide in a dose of 5 mg/k
g i.a. had no significant effect on vasoconstrictor responses to U4661
9, norepinephrine or angiotensin II. Hindquarters vasodilator response
s to levcromakalim, but not to nitric oxide, were decreased significan
tly following administration of glibenclamide. These data suggest that
glibenclamide, in addition to inhibiting K+-ATP channels, has thrombo
xane A(2) receptor blocking activity in the pulmonary vascular bed of
the cat. These data also suggest that vasoconstrictor responses to U46
619 may be mediated by different thromboxane A(2) receptors with diffe
rent binding affinities in the pulmonary and in the hindquarters vascu
lar beds of the cat. (C) 1997 Elsevier Science B.V.