Titre du document / Document title

Differential effects of glibenclamide on responses to thromboxane A2 mimic, U46619, in the pulmonary and hindquarters vascular beds of the cat

Auteur(s) / Author(s)

KAYE A. D. ^{(1 2 3)} ; NOSSAMAN B. D. ^{(1 2 3)} ; SANTIAGO J. A. ^{(1 2 3)} ; DEWITT B. J. ^{(1 2 3)} ; IBRAHIM I. N. ^{(1 2 3)} ; KADOWITZ P. J. ^{(1 2 3)} ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Anesthesiology, Tulane University Medical Center, New Orleans, LA 70112-2699, ETATS-UNIS
⁽²⁾ Department of Pharmacology, Tulane University Medical Center, New Orleans, LA 70112-2699, ETATS-UNIS
⁽³⁾ Deparment of Anesthesiology and Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, ETATS-UNIS

Résumé / Abstract

The inhibitory effects of the oral sulfonylurea, glibenclamide, on vasoconstrictor responses to the thromboxane A₂ mimic. U46619, were investigated in the pulmonary and hindquarters vascular beds of the cat under constant flow conditions. When lobar arterial tone was at resting conditions (14 ± 2 mm Hg). intralobar injections of U46619, prostaglandin F_2α, prostaglandin D₂, angiotensin II. norepinephrine, and BAY K 8644 caused dose-related increases in lobar arterial pressure without altering left atrial pressure. Following an intralobar infusion of glibenclamide (5 mg/kg), vasoconstrictor responses to U46619, prostaglandin F_2α and prostaglandin D₂ were significantly reduced, whereas vasoconstrictor responses to norepinephrine and angiotensin II were not altered and responses to BAY K 8644 were significantly enhanced. When tone in the pulmonary vascular bed was raised to a high steady level (36 ± 3 mm Hg), glibenclamide in a dose of 5 mg/kg i.a. markedly attenuated responses to injections of U46619 and reduced the vasodilator responses to the K⁺-ATP channel opener, levromakalim, whereas responses to acetylcholine and S-nitroso-N-acetylpenicillamine (SNAP). a nitric oxide donor, were not changed. In the hindquarters vascular bed of the cat, administration of glibenclamide in a dose of 5 mg/kg i.a. had no significant effect on vasoconstrictor responses to U46619, norepinephrine or angiotensin II. Hindquarters vasodilator responses to levecromakalim, but not to nitric oxide, were decreased significantly following administration of glibenclamide. These data suggest that glibenclamide, in addition to inhibiting K⁺-ATP channels. has thromboxane A₂ receptor blocking activity in the pulmonary vascular bed of the cut. These data also suggest that vasoconstrictor responses to U46619 may be mediated by different thromboxane A₂ receptors with different binding affinities in the pulmonary and in the hindquarters vascular beds of the cat.

Revue / Journal Title

European journal of pharmacology   ISSN 0014-2999   CODEN EJPHAZ 

Source / Source

1997, vol. 340, n^o2-3, pp. 187-193 (22 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1967) (Revue)

Mots-clés anglais / English Keywords

Glibenclamide ; Mechanism ; Thromboxane A2 ; Muscle contraction ; Smooth muscle ; Blood vessel ; Circulatory system ; Pulmonary vein ; Pulmonary artery ; Lung ; Regulation(control) ; Vasoconstriction ; Animal ; Cat ; Ionic channel ; Potassium ; Sulfonylureas ; Biological receptor ; Fissipedia ; Carnivora ; Mammalia ; Vertebrata ; Arachidonic acid derivatives ;

Mots-clés français / French Keywords

Glibenclamide ; Mécanisme ; Thromboxane A2 ; Contraction musculaire ; Muscle lisse ; Vaisseau sanguin ; Appareil circulatoire ; Veine pulmonaire ; Artère pulmonaire ; Poumon ; Régulation ; Vasoconstriction ; Animal ; Chat ; Canal ionique ; Potassium ; Sulfonylurées ; Récepteur biologique ; U 46619 ; Fissipedia ; Carnivora ; Mammalia ; Vertebrata ; Arachidonique acide dérivé ;

Mots-clés espagnols / Spanish Keywords

Glibenclamida ; Mecanismo ; Tromboxano A2 ; Contracción muscular ; Músculo liso ; Vaso sanguíneo ; Aparato circulatorio ; Vena pulmonar ; Arteria pulmonar ; Pulmón ; Regulación ; Vasoconstricción ; Animal ; Gato ; Canal iónico ; Potasio ; Sulfonilureas ; Receptor biológico ; Fissipedia ; Carnivora ; Mammalia ; Vertebrata ; Araquidónico ácido derivado ;

Localisation / Location

INIST-CNRS, Cote INIST : 13322, 35400007986855.0110