The effects of agents that bind to cytochrome P-450 on hypoxic pulmonary vasoconstriction

J. T. Sylvester, C. McGowan

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


The relationship between pulmonary arterial pressure (Ppa) and blood flow (Q) was determined during normoxia and hypoxia in ventilated pig lungs perfused in situ with the animal's own blood. Hypoxia shifted the Ppa-Q relationship to the right and decreased its slope, indicating pulmonary vasoconstriction. Carbon monoxide (11.5% in the inspired gas) and metyrapone ditartrate (10 mg/min into the perfusate) caused vasodilation when oxygenation was normal and reduced the vasoconstriction caused by hypoxia. Since the only pharmacological property CO and metyrapone are thought to have in common at the concentrations employed is the ability to bind to the heme iron of cytochrome P-450, these results are consistent with the hypothesis that desaturation of this cytochrome leads to pulmonary vasoconstriction. Prostaglandin F(2α), infused into the pulmonary artery at 0.01 mg/min, when oxygenation was normal, had effects on the Ppa-Q relationship similar to those of hypoxia. The F(2α) response was also reduced by CO and metyrapone, suggesting either that P-450 was involved in the F(2α) response or that CO and metyrapone were toxic to pulmonary vascular smooth muscle. Proadifen hydrochloride (1 mg/min), which is thought to bind to the protein moiety of P-450, also reduced the hypoxic response, but was a vasoconstrictor during normoxia and did not affect the F(2α) response.

Original languageEnglish (US)
Pages (from-to)429-437
Number of pages9
JournalCirculation research
Issue number3
StatePublished - 1978
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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