Potassium channel blockade and halothane vasodilation in conducting and resistance coronary arteries.
On the basis of reports that volatile anesthetics, such as halothane, open membrane potassium channels in several tissues, it was investigated whether coronary vasodilation by halothane is mediated by a similar mechanism. The ability of glyburide, a blocker of ATP-sensitive K+ (KATP) channels, and tetraethylammonium (TEA+), a blocker of Ca(2+)-activated K+ channels, to modify halothane-induced vasodilation was assessed in two vascular preparations. First, coronary resistance vessel tone was measured in isolated rat hearts arrested with tetrodotoxin and, second, conducting vessel responsiveness was evaluated in ring segments of the porcine epicardial coronary artery contracted with prostaglandin F2 alpha. Halothane alone markedly vasodilated the perfused hearts and attenuated the agonist contraction of the coronary rings. Blockade of KATP channels with glyburide alone did not affect the base-line vascular tone or responsiveness but it inhibited cromakalim vasodilation. TEA+ alone caused vasoconstriction. In hearts perfused at constant pressure, glyburide significantly attenuated the halothane-induced increase in coronary flow by 56% and perfusion with a high K+ buffer reduced the halothane-induced vasodilation response by 94%. In endothelium-denuded coronary rings, glyburide did not affect halothane-induced relaxation but KATP channel blockade potentiated halothane-caused relaxation in endothelium-intact rings. The attenuation of halothane-induced vasodilation by TEA+ seen in the perfused hearts did not achieve statistical significance and no halothane/TEA+ interaction was evident in the coronary rings. Thus, the data from the perfused heart experiments suggest that halothane relaxes rat coronary resistance vessels, in part, by opening K+ channels.
Larach
D R
DR
Department of Anesthesia, College of Medicine, Pennsylvania State University, Hershey.
Schuler
H G
HG
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D019806:Cromakalim; D004730:Endothelium, Vascular / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D001578:Benzopyrans; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D013757:Tetraethylammonium Compounds; D019806:Cromakalim; D005905:Glyburide; D006221:Halothane