Glibenclamide inhibits thromboxane-mediated vasoconstriction by thromboxane receptor blockade.
Vascul Pharmacol
; 40(6): 285-92, 2004 Jan.
Article
em En
| MEDLINE
| ID: mdl-15063832
ABSTRACT
Because sulfonylureas, such as glibenclamide, are used to treat Type 2 diabetes and because this disease is associated with various cardiovascular complications that may be mediated by thromboxane (TX), this study was designed to characterize the role of glibenclamide on TX-mediated contractions in isolated ring segments of bovine coronary arteries and rabbit aortas. A series of TXA(2) analogs [9,11 Dideoxy-9alpha, 11alpha-methanoepoxy prostaglandin F(2alpha) (U46619), [1S-(1alpha, 2beta(5Z),3alpha(1E, 3R*),4alpha)]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo [2.2.1]heptan-2-yl]-5-heptenoic acid (I-BOP), carbocyclic TXA(2) (CTA(2)) and 9,11-dideoxy-9alpha,11alpha-epoxymethano prostaglandin F(2alpha) (U44069)], endothelin and phenylephrine contracted both types of blood vessels. Glibenclamide (10 microM) inhibited the contraction to each of the TX agonists but had no effect on endothelin- or phenylephrine-induced contractions. We hypothesized that this effect was due to a direct effect to block the vascular smooth muscle cell TX receptor. Receptor binding studies were performed in rabbit vascular smooth muscle cells and indicated that glibenclamide (10 microM) inhibited (125)I-BOP binding by more than 80%. The inhibition constants or K(i) for glibenclamide was 0.53 microM. These studies provide the first evidence that the ability of glibenclamide to inhibit TX-mediated contractions occurs independent of the vascular K(ATP) channel and is, instead, mediated by the blockade of the vascular TX receptor.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Tromboxano A2
/
Vasoconstrição
/
Vasoconstritores
/
Glibureto
/
Receptores de Tromboxanos
Limite:
Animals
Idioma:
En
Revista:
Vascul Pharmacol
Assunto da revista:
ANGIOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos