Glibenclamide inhibits thromboxane A2-induced contraction in human internal mammary artery and saphenous vein.
Glibenclamide, like other hypoglycemic sulfonylurea derivatives, is a potent blocker of ATP-regulated K+ channels. In addition, it is reported to inhibit prostanoid-induced contractions of isolated vascular smooth muscle from different animal species. We investigated the effect of glibenclamide on the thromboxane A2-mimetic U-46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy-prostaglandin F2alpha)-induced contractions in human isolated internal mammary arteries and saphenous veins. In the two vascular preparations, glibenclamide (3, 10 and 30 microM) caused a concentration-dependent shift to the right of the U-46619 contraction-response curve with a reduction, at the highest concentrations, in the maximal responses. This inhibitory effect appears selective for thromboxane A2-induced contractions since glibenclamide (30 microM) did not alter the contraction of internal mammary arteries in response to norepinephrine and of saphenous veins in response to 5-hydroxytryptamine (5-HT) and endothelin-1. However, glibenclamide reduced the endothelin-1-induced contraction in internal mammary arteries. The endothelin-1-induced contractions were similarly inhibited by GR 32191 ([1R-[1alpha(Z),2beta,3beta,5alpha]]-(+)-7-[5-([1,1'-b iphenyl]-4-ylmethoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-++ +heptonoic acid, a thromboxane A2 receptor antagonist. These results suggest that glibenclamide also reduced the endothelin-1-induced contractions by inhibiting a thromboxane A2 receptor-mediated component of the contraction elicited by this peptide. In conclusion, glibenclamide clearly appears to exert a specific inhibitory influence on prostanoid-induced contractions in human internal mammary arteries and saphenous veins.
Stanke
F
F
Laboratory of Pharmacology, PCEBM, Faculté de Médecine, La Tronche, France.
Cracowski
J L
JL
Chavanon
O
O
Magne
J L
JL
Blin
D
D
Bessard
G
G
Devillier
P
P
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000008:administration & dosage / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008323:Mammary Arteries / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology; D013928:Thromboxane A2 / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology
D001713:Biphenyl Compounds; D019332:Endothelin-1; D006538:Heptanoic Acids; D007004:Hypoglycemic Agents; D011448:Prostaglandin Antagonists; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; D012701:Serotonin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C060013:vapiprost; D005905:Glyburide; D009638:Norepinephrine