Relaxant effect of levcromakalim in isolated human small subcutaneous arteries

• Published in: European journal of pharmacology Vol. 287; no. 3; pp. 313 - 316
• Main Authors: Hüsken, Birgitta C.P., Vroom, Margreet B., Timmenga, Erik-Jan F., Pfaffendorf, Martin, Van Zwieten, Pieter A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 20-12-1995; Elsevier
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenosine Triphosphate - pharmacology; Adolescent; Adult; Arteries - drug effects; Artery, subcutaneous; Benzopyrans - pharmacology; Biological and medical sciences; Cardiovascular system; Cromakalim; Dose-Response Relationship, Drug; Drug Interactions; Female; Glibenclamide; Glyburide - pharmacology; Human; Humans; In Vitro Techniques; Levcromakalim; Medical sciences; Methacholine Chloride - pharmacology; Middle Aged; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Pharmacology. Drug treatments; Potassium Channels - drug effects; Prostaglandin Endoperoxides, Synthetic - pharmacology; Pyrroles - pharmacology; Skin - blood supply; Thromboxane A2 - analogs & derivatives; Thromboxane A2 - pharmacology; Vasoconstrictor Agents - pharmacology; Vasodilator agents. Cerebral vasodilators; Human; Artery, subcutaneous; Levcromakalim; Glibenclamide; Agonist; Vasodilator agent; Ionic channel; Subcutaneous tissue; In vitro; Potassium; Artery
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(95)00714-8

The effect of levcromakalim, an ATP-sensitive K
+ channel opener, on isolated subcutaneous arteries from mammary tissues obtained from female patients undergoing reconstructive breast surgery was investigated. The small arteries were preserved in the University of Wisconsin (UW) solution. The contractile responses to K
+ and 9,11-dideoxy-11α,9α-epoxy-methano-prostaglandin F
2α (U46619) and the relaxant responses to levcromakalim and to the endothelium-dependent vasodilator, methacholine, in these arteries remained fully intact after preservation in UW solution for at least 5 days. The pD
2 value and maximal relaxation obtained from the concentration-response curve of levcromakalim (
n = 7) were 5.78 ± 0.23 and 81 ± 6%, respectively. The vasodilator effect of levcromakalim was significantly antagonised by the ATP-sensitive K
+ channel blocker, glibenclamide (1 and 3 μM). In conclusion, isolated human arteries contain ATP-sensitive K
+ channels, which can be modulated by K
+ channel openers and blockers. Subcutaneous small arteries, as used in our experiments, appear to be very suitable for pharmacological experiments.