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, traditionally inhalational anesthetics have been shown to attenuate hypoxic pulmonary vasoconstriction and have therefore been considered pulmonary 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 vasoconstriction produced by halothane. The purpose of this study was to test the hypothesis that the halothane-induced contraction was caused by the release of sarcoplasmic reticular Ca++. Isometric tension was measured in isolated rings of bovine pulmonary artery with intact endothelium. Three protocols were followed. Rings were exposed to cyclopiazonic acid or ryanodine (modulators of sarcoplasmic reticular Ca++) (protocol 1), caffeine (protocol 2) verapamil or nicardipine (protocol 3). Halothane-induced contraction was measured before, during and after exposure to drug. In nominally Ca(++)-free buffer cyclopiazonic acid and ryanodine attenuated the halothane-induced contraction. Similar responses 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-induced contraction. Our data in bovine pulmonary artery segments are consistent with halothane effects seen in vascular smooth muscle from several other tissues and species. The results of our experiments support the conclusion that the release of intracellular Ca++ from sarcoplasmic reticular stores is responsible for the halothane-induced vasoconstriction that has been observed in this tissue.
Fehr
D M
DM
Department of Anesthesia, Pennsylvania State University, College of Medicine, Hershey, USA.
Larach
D R
DR
Zangari
K A
KA
Schuler
H G
HG
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002417:Cattle; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D011188:Potassium / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D002110:Caffeine; D011188:Potassium; D002118:Calcium; D006221:Halothane