Glibenclamide inhibits hypoxic relaxation of isolated porcine coronary arteries under conditions of impaired glycolysis.
The possible involvement of ATP-sensitive K+ channels (KATP) in hypoxic relaxation of isolated porcine coronary arteries was investigated. Tubular segments taken from the left anterior descending artery were suspended in myographs for recording of isometric contractile force. Hypoxia (pO2 = 20.3 mm Hg +/- 0.5) produced a greater relaxation in preparations contracted by 30 mM K+ (49.7% +/- 7.2) compared with 124 mM K+ (19.9% +/- 2.2) which is compatible with the involvement of K+ channel activation in the mechanism of hypoxic relaxation. In a normal glucose-containing Krebs solution the KATP blocker glibenclamide (1 microM) failed to influence the hypoxic relaxation of preparations contracted by the thromboxane A2 analogue U-46619. Under conditions created to inhibit non-oxidative ATP production from glycolysis using a glucose-free Krebs solution containing 2-deoxyglucose (10 mM), the hypoxic relaxation was enhanced from 54.5% +/- 5.0 to 77.2% +/- 4.4. Under these conditions glibenclamide (1 microM) significantly inhibited the hypoxic relaxant response from 77.2% +/- 4.2 to 55.2% +/- 4.4 and prolonged the time until half-maximal relaxation from 5.5 min +/- 0.6 to 8.1 min +/- 0.6. A low concentration of the KATP opener levcromakalim (30 nM) failed to significantly potentiate the hypoxic relaxation. The adenosine receptor blocker theophylline (1 microM) or removal of the endothelium showed no effect on the hypoxic relaxation. In normal glucose-containing Krebs solution, indomethacin (10 microM) caused a small but significant inhibition of the hypoxic relaxation from 54.5% +/- 5.0 to 41.6% +/- 3.6.(ABSTRACT TRUNCATED AT 250 WORDS)
Mellemkjaer
S
S
Institute of Pharmacology, University of Aarhus, Denmark.
Nielsen-Kudsk
J E
JE
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D019806:Cromakalim; D003847:Deoxyglucose / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D013552:Swine; D013806:Theophylline / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D011450:Prostaglandin Endoperoxides, Synthetic; D011758:Pyrroles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D013806:Theophylline; D005905:Glyburide; D007213:Indomethacin