Relaxant effect of levcromakalim in isolated human small subcutaneous arteries.
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-11a,9a-epoxy-methano-prostaglandin F2 alpha (U46619) and the relexant 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 pD2 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 microM). 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.
Hüsken
B C
BC
Department of Pharmacotherapy, University of Amsterdam, Netherlands.
Vroom
M B
MB
Timmenga
E J
EJ
Pfaffendorf
M
M
Van Zwieten
P A
PA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D001158:Arteries / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D001578:Benzopyrans; D015221:Potassium Channels; D011450:Prostaglandin Endoperoxides, Synthetic; D011758:Pyrroles; D014662:Vasoconstrictor Agents; D019806:Cromakalim; D016210:Methacholine Chloride; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D005905:Glyburide