Faculty Collaboration Database

Glibenclamide inhibits thromboxane-mediated vasoconstriction by thromboxane receptor blockade. Vascul Pharmacol 2004 Jan;40(6):285-92

Date

04/06/2004

Pubmed ID

15063832

DOI

10.1016/j.vph.2004.02.001

Scopus ID

2-s2.0-1842424855 (requires institutional sign-in at Scopus site)   13 Citations

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.

Author List

Pfister SL, Pratt PE, Kurian J, Campbell WB

Authors

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Sandra L. Pfister PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Adenosine Triphosphate
Animals
Aorta, Thoracic
Bridged Bicyclo Compounds, Heterocyclic
Cattle
Coronary Vessels
Fatty Acids, Unsaturated
Glyburide
In Vitro Techniques
Male
Muscle, Smooth, Vascular
Potassium Channels
Prostaglandin Endoperoxides, Synthetic
Rabbits
Radioligand Assay
Receptors, Thromboxane
Thromboxane A2
Vasoconstriction
Vasoconstrictor Agents