Differential effects of sulfonylurea derivatives on vascular ATP-sensitive potassium channels
| Autor: | Helene L.M. Siero, Richard Engbersen, Paul Smits, Miek M. Moons, Rosalinde Masereeuw, Frans G. M. Russel, Miriam A. van Gestel |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle ATP-sensitive potassium channel Pharmacology Kidney Rats Inbred WKY Muscle Smooth Vascular Glibenclamide chemistry.chemical_compound Phenylephrine Renal Artery KATP Channels Internal medicine medicine Animals Mesenteric arteries Cardiovascular diseases [NCEBP 14] Dose-Response Relationship Drug business.industry Potassium channel Mesenteric Arteries Rats Vasodilation Glimepiride Membrane transport and intracellular motility Renal disorder [NCMLS 5] Endocrinology medicine.anatomical_structure Sulfonylurea Compounds chemistry Vasoconstriction Pinacidil business Myograph medicine.drug |
| Zdroj: | European Journal of Pharmacology, 681, 1-3, pp. 75-9 European Journal of Pharmacology, 681, 75-9 |
| ISSN: | 1879-0712 0014-2999 |
| Popis: | Contains fulltext : 110913.pdf (Publisher’s version ) (Closed access) Sulfonylurea drugs exert their insulinotropic action by inhibiting ATP-sensitive potassium channels in the pancreas. However, these channels are also expressed in myocardial and vascular smooth muscle, implicating possible detrimental cardiovascular effects. Aim of the present study was to investigate the inhibitory potency of various widely used sulfonylurea drugs in resistance arteries. Isolated mesenteric and renal resistance arteries mounted in a myograph and isolated perfused kidneys were used to measure drug responses. Pinacidil induced a dose-dependent relaxation of phenylephrine preconstricted mesenteric and renal arteries (pEC(50)=6.10 +/- 0.01 and 5.66 +/- 0.03, respectively). Schild plot analysis of pinacidil relaxation curves in mesenteric arteries in the presence of sulfonylurea antagonists revealed the following order of potency: glimepiride (pA(2)=7.22) >/= glibenclamide (pA(2)=7.05) > glipizide (pA(2)=5.25) > gliclazide (pA(2)=4.31). The effects of glibenclamide in renal arteries were comparable. Furthermore, glibenclamide produced similar constrictive properties in isolated renal arteries as in isolated perfused whole kidneys. We conclude that sulfonylurea drugs exert differential effects on vascular smooth muscle K(ATP) channels. Our results suggest that glibenclamide and glimepiride will interact with these channels at therapeutic concentrations. |
| Databáze: | OpenAIRE |
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