Barbiturate anesthetics inhibit thromboxane-, potassium-, but not angiotensin-induced pulmonary vasoconstriction.
Administration of the oxidant lipid peroxide tertiary butyl hydroperoxide (t-bu-OOH) in the isolated rabbit lung leads to acute pulmonary vasoconstriction, which is caused by the synthesis of thromboxane. The inhalational anesthetics, halothane, nitrous oxide, and cyclopropane, markedly enhance t-bu-OOH-induced pulmonary vasoconstriction and thromboxane production. The effects of the intravenous (iv) barbiturates thiopental and pentobarbital on t-bu-OOH-induced vasoconstriction were studied. Thiopental completely and pentobarbital partially blocked t-bu-OOH-induced vasoconstriction. Thiopental inhibited t-bu-OOH-induced synthesis of thromboxane and prostacyclin but pentobarbital did not. This inhibitory action of thiopental may be due to its antioxidant properties because similar inhibition has been observed of t-bu-OOH-induced thromboxane production with the antioxidants, vitamin E, or butylated hydroxylanisole. Thiopental and pentobarbital also inhibited the vasoconstriction induced by a thromboxane analog, epoxymethano prostaglandin H2 (U46619). Finally, both barbiturates partially inhibited the pulmonary vasoconstriction caused by potassium chloride, which requires calcium entry, but they did not inhibit the constriction caused by angiotensin II, which does not require calcium entry. These results suggest that pentobarbital and thiopental may block pulmonary vasoconstriction by inhibiting calcium entry.
McShane
A J
AJ
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland.
Crowley
K
K
Shayevitz
J R
JR
Michael
J R
JR
Adkinson
N F
NF
Traystman
R J
RJ
Gurtner
G H
GH
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D010545:Peroxides / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000037:antagonists & inhibitors*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors; D011817:Rabbits; D013874:Thiopental / Q000494:pharmacology; D013931:Thromboxanes / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects*; D020122:tert-Butylhydroperoxide
D001463:Barbiturates; D010545:Peroxides; D011450:Prostaglandin Endoperoxides, Synthetic; D013931:Thromboxanes; D000804:Angiotensin II; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D020122:tert-Butylhydroperoxide; D010424:Pentobarbital; D013874:Thiopental