TY  - JOUR
PY  - 1992//
TI  - Intact lung cytochrome P-450 is not required for hypoxic pulmonary vasoconstriction
JO  - American journal of physiology
A1  - Chang, S. W.
A1  - Dutton, D.
A1  - Wang, H. L.
A1  - He, L. S.
A1  - Stearns, R.
A1  - Hui, A.
A1  - Giacomini, K. M.
A1  - Ortiz de Montellano, P.
A1  - Voelkel, N. F.
SP  - L446
EP  - 453
VL  - 263
IS  - 4 Pt 1
N2  - 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.<p /> <p>Language: en</p>
LA  - en
SN  - 0002-9513
UR  - http://dx.doi.org/10.1152/ajplung.1992.263.4.L446
ID  - ref1
ER  -