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Citation |
Chang SW, Dutton D, Wang HL, He LS, Stearns R, Hui A, Giacomini KM, Ortiz de Montellano P, Voelkel NF. Am. J. Physiol. 1992; 263(4 Pt 1): L446-453. |
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Copyright |
(Copyright © 1992, American Physiological Society) |
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DOI |
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PMID |
1415722 |
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Abstract |
Lung cytochrome P-450 has been suggested to play a role in hypoxic pulmonary vasoconstriction. We reexamined this hypothesis using specific suicide substrate inhibitors of cytochrome P-450, 1-aminobenzotriazole (1-ABT), and chloramphenicol. In isolated, blood-perfused rat lungs, 1-ABT (0.5 mg/ml) and chloramphenicol (1 mg/ml) inhibited lung microsomal cytochrome P-450 (ethoxycoumarin O-deethylase) activity to 24 and 44% of control, respectively, and blunted hypoxia and angiotensin II-induced vasoconstriction. The depression of vascular contraction by 1-ABT was not due to an effect on calcium channels, since similar concentrations of 1-ABT had no inhibitory activity on electrical field-stimulated contractile response in rabbit papillary muscle strips. However, when 1-ABT was washed out of the lung after preincubation, the vascular reactivity to hypoxia and angiotensin II was restored despite persistent depression of lung cytochrome P-450 activity to 26% of control values. In isolated rat aortic and pulmonary arterial rings, addition of 1-ABT or metyrapone to the organ bath acutely reversed norepinephrine-induced contraction but preincubation with 1-ABT, metyrapone, or chloramphenicol had no effect on subsequent norepinephrine contractions. We conclude that 1-ABT inhibited lung vascular reactivity by a mechanism independent of cytochrome P-450 inhibition or calcium channel blockade and that an intact lung cytochrome P-450 system is not required for hypoxic pulmonary vasoconstriction in rat lungs. Language: en |
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Keywords |
Angiotensin II; Animals; Aorta; Chloramphenicol; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Electric Stimulation; Hypoxia; In Vitro Techniques; Lung; Male; Metyrapone; Papillary Muscles; Pulmonary Circulation; Rabbits; Rats; Triazoles; Vasoconstriction |