DUAL ACTIONS OF HALOTHANE ON INTRACELLULAR CALCIUM STORES OF VASCULARSMOOTH-MUSCLE

Background: Halothane has been reported to affect the integrity of int racellular Ca2+ stores in a number of tissues including vascular smoot h muscle. However, the actions of halothane on intracellular Ca2+ stor es are not yet fully understood. Methods: Employing the isometric tens ion recording method, the action of halothane in isolated endothelium- denuded rat mesenteric arteries under either intact or beta-escin-memb rane-permeabilized conditions was investigated. Results: Halothane (0. 125-596) produced concentiation-dependent contractions in Ca2+ free so lution in both intact and membrane-permeabilized muscle strips. Ryanod ine treatment or repetitive application of phenylephrine eliminated bo th caffeine- and halothane-induced contractions in the Ca2+ free solut ion. When either halothane and caffeine, caffeine and halothane, pheny lephrine and halothane, or inositol 1,4,5-triphosphate and halothane w ere applied consecutively in the Ca2+ free solution in either intact o r membrane-permeabilized muscle strips, the contraction induced by app lication of the second agent of the pair was inhibited compared to app lication of that agent alone. However, when procaine was applied befor e and during application of the first agent, the contraction induced b y the first agent was inhibited and the contraction induced by the sec ond agent was restored. Heparin inhibited the inositol 1,4,5-triphosph ate-mediated contraction, but not contractions induced by halothane or caffeine. Halothane (0.125-5%), applied during Ca2+ loading, produced concentration-dependent inhibition of the caffeine contraction (used to estimate the amount of Ca2+ in the store) in both intact and membra ne-permeabilized muscle strips. In contrast, halothane applied with pr ocaine during Ca2+ lending produced concentration-dependent enhancemen t of the caffeine contraction. This enhancement was observed only In t he Intact but not in the membrane-permeabilized condition. Conclusions : Halothane has two distinct actions on the intracellular Ca2+ stores of vascular smooth muscle, a Ca2+ releasing action and a stimulating a ction on Ca2+ uptake. Halothane releases Ca2+ from the stores that are sensitive to both caffelne/ryanodine and phenylephrine/inositol 1,4,5 -triphosphate through a precaine-sensitive mechanism. The observed inh ibitory effect on Ca2+ uptake is probably caused by the Ca2+ releasing action, whereas the stimulating action on Ca2+ uptake after blockade of Ca2+ release may be membrane-mediated.