EFFECT OF K+ CHANNEL BLOCKADE WITH TETRAETHYLAMMONIUM ON ANESTHETIC-INDUCED RELAXATION IN CANINE CEREBRAL AND CORONARY-ARTERIES

The mechanism by which volatile anesthetics produce their direct effects on vascular smooth muscle remains unknown. The authors previously reported that volatile anesthetics decrease both Ca2+ and K+ currents, however the role of Ca2+-activated K+ channels during the vasorelaxation by anesthetics has not been investigated. The purpose of this study was to determine whether blockade of the K+ channel alters the response to volatile anesthetics. Responses were studied in canine middle cerebral arteries and proximal and distal canine coronary arteries. Vascular rings (2-mm length) were suspended in tissue baths, and isometric tension was recorded. Rings were constricted with 40 mM KCl and prostaglandin F2alpha (middle cerebral arteries only) and subsequently exposed to enflurane (3.25%), halothane (1.35%), and isoflurane (2.1%). Volatile anesthetics produced vasorelaxation with relative potency in order: enflurane > halothane > isoflurane. The procedure was repeated in the presence of the K+ channel blocker tetraethylammonium chloride (TEA, 20 mM). In all groups of vessels TEA alone elicited either no increase or only a transient increase in tension, however constrictions to both agonists were augmented in the presence of TEA. The presence of TEA significantly augmented anesthetic-induced vasorelaxation in small and large coronary vessels and in middle cerebral arteries. However, this effect was more pronounced in the cerebral as compared to coronary arteries. Constrictions produced in cerebral vessels by 15 muM prostaglandin F2alpha were comparable with constrictions produced by 5 muM prostaglandin F2alpha in the presence of TEA. The subsequent relaxant response of these vessels to enflurane was also comparable in the two groups. This finding suggests that the augmented relaxant response to enflurane in the presence of TEA was independent of the associated increase in agonist-induced contraction. These results demonstrate that: 1) volatile anesthetics induce relaxation of preconstricted isolated canine middle cerebral arteries and coronary arteries; 2) the middle cerebral arteries are more sensitive than coronary arteries to the dilating effects of volatile anesthetics; and 3) K+ channel blockade potentiates the vasorelaxing effects of volatile anesthetics.