Inhalation anesthetics augment oxidant-induced pulmonary vasoconstriction: evidence for a membrane effect.
Inhalational anesthetics "fluidize" biologic membranes. Since arachidonate metabolism also occurs in cell membranes, anesthetic agents may modify arachidonic acid mediator production. The authors used the isolated perfused rabbit lung preparation to examine the effects of inhalational anesthetics on the production of arachidonate mediators. The oxidant tert-butyl-hydroperoxide (t-bu-OOH) is known to cause pulmonary vasoconstriction by causing increased production of thromboxane A2 (TxA2). The authors administered three anesthetics (halothane, cyclopropane, and nitrous oxide) of widely different potencies, at different dosages, each to three different groups of preparations and challenged the lungs at each anesthetic dose with t-bu-OOH. They found a dose-related augmentation of the pulmonary vasopressor response to t-bu-OOH. Preparations given t-bu-OOH alone showed no change in response over time. Lungs perfused with indomethacin (5 micrograms . ml-1 in Krebs-Henseleit buffer), ventilated with cyclopropane (2 MAC), and challenged with t-bu-OOH showed almost complete inhibition of the response to t-bu-OOH. Indomethacin at this concentration is a specific inhibitor of cyclooxygenase. The authors also have demonstrated significantly increased perfusate levels of thromboxane B2 (TxB2), the inactive metabolite of TxA2, after oxidant challenge during exposure to 2% halothane compared with TxB2 levels before halothane exposure. The authors believe that the augmented pressor response and mediator production occur because of increased substrate (arachidonic acid) availability induced by anesthetic agent.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000704:Analysis of Variance; D000769:Anesthesia, Inhalation; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D006221:Halothane / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010545:Peroxides / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D013929:Thromboxane B2 / Q000096:biosynthesis; D014661:Vasoconstriction / Q000187:drug effects*; D020122:tert-Butylhydroperoxide
D000777:Anesthetics; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D010545:Peroxides; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D020122:tert-Butylhydroperoxide; D006221:Halothane; D007213:Indomethacin