HALOTHANE CONSTRICTS BOVINE PULMONARY-ARTERIES BY RELEASE OF INTRACELLULAR CALCIUM

In the canine lung, when compared with the conscious state, halothane causes vasoconstriction that is independent of blood flow. However, tr aditionally inhalational anesthetics have been shown to attenuate hypo xic pulmonary vasoconstriction and have therefore been considered pulm onary vasodilators. We have shown, in isolated bovine pulmonary artery , that halothane produces a transient contractile response, A variety of smooth muscle cellular mechanisms could be responsible for the vaso constriction produced by halothane. The purpose of this study was to t est the hypothesis that the halothane-induced contraction was caused b y the release of sarcoplasmic reticular Ca++. Isometric tension was me asured in isolated rings of bovine pulmonary artery with intact endoth elium. Three protocols were followed. Rings were exposed to cyclopiazo nic acid or ryanodine (modulators of sarcoplasmic reticular Ca++) (pro tocol 1), caffeine (protocol 2) and verapamil or nicardipine (protocol 3). Halothane-induced contraction was measured before, during and aft er exposure to drug. In nominally Ca++-free buffer cyclopiazonic acid and ryanodine attenuated the halothane-induced contraction. Similar re sponses were seen with cyclopiazonic acid and ryanodine treatment when caffeine was substituted for halothane. The calcium channel blockers nicardipine and verapamil did not significantly alter the halothane-in duced contraction. Our data in bovine pulmonary artery segments are co nsistent with halothane effects seen in vascular smooth muscle from se veral other tissues and species. The results of our experiments suppor t the conclusion that the release of intracellular Ca++ from sarcoplas mic reticular stores is responsible for the halothane-induced vasocons triction that has been observed in this tissue.