Differential effects of sulphonylureas on the vasodilatory response evoked by K(ATP) channel openers.
The potency of three sulphonylureas, glibenclamide, glimepiride and gliclazide in antagonizing the vasorelaxant action of openers of adenosine triphosphate (ATP)-regulated K+ channel (KATP) was studied in vivo and in vitro in micro- and macrovessels, respectively. In the hamster cheek pouch, the vasodilatation and the increase in vascular diameter and blood flow induced by diazoxide were markedly reduced by the addition of either glibenclamide or glimepiride (0.8 microm) while they were not affected by gliclazide up to 12 microm. Similarly, in rat and guinea-pig isolated aortic rings, glibenclamide, glimepiride and gliclazide reduced the vasodilator activity of cromakalim. However, the inhibitory effect of gliclazide was considerably less when compared with either glimepiride or glibenclamide. These results suggest that, in contrast to glibenclamide and glimepiride, therapeutically relevant concentrations of gliclazide do not block the vascular effects produced by KATP channel openers in various in vitro and in vivo animal models.
Ravel
Denis
D
Institut de Recherches Internationales Servier, Courbevoie, France.
Levens
Nigel
N
Félétou
Michel
M
Néliat
Gervais
G
Auclair
Jean
J
Bouskela
Eliete
E
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D019806:Cromakalim / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003981:Diazoxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D005907:Gliclazide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008297:Male; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D014665:Vasodilator Agents; D019806:Cromakalim; C057619:glimepiride; D000255:Adenosine Triphosphate; D005907:Gliclazide; D003981:Diazoxide; D005905:Glyburide