Inhibition of nitric oxide synthesis results in a selective increase in arterial resistance in rabbit lungs

R. S. Sprague, A. H. Stephenson, R. A. Dimmitt, N. L. Weintraub, C. A. Branch, L. McMurdo, A. J. Lonigro

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Endogenous nitric oxide (NO) opposes the vasoconstricton that occurs when lungs are ventilated with a hypoxic gas mixture. However, the contribution of NO to pulmonary vascular resistance when alveolar gas tension is not reduced remains to be defined. Here, we investigated the hypothesis that endogenous NO is a determinant of pulmonary vascular resistance in isolated perfused rabbit lungs ventilated with a normoxic gas mixture. Moreover, we wished to establish that, as flow rate increases, the contribution of NO to vascular resistance increases. In addition, we examined the contribution of NO to the longitudinal distribution of pulmonary vascular resistance. Pressure-flow curves were generated in isolated blood perfused rabbit lungs by varying flow rate from 50 ml/min to 300 ml/min in the presence and absence of the cyclooxygenase inhibitor, indomethacin (100 μM) and the inhibitor of NO synthesis, N(G)-nitro-L-arginine methyl ester (L-NAME, 100 μM). Indomethacin did not alter total pulmonary vascular resistance or the longitudinal distribution of resistance. In contrast, L-NAME administration resulted in significant, flow-related increases in total vascular resistance, i.e, after L-NAME, as flow rate increased, the increment in resistance increased. L-NAME-induced increases in total pulmonary vascular resistance were the result of flow-related increases in the arterial component of vascular resistance. These results provide support for the hypothesis that NO is an important determinant of pulmonary vascular resistance in the rabbit and that the major site of NO activity resides in the arterial side of that circulation.

Original languageEnglish (US)
Pages (from-to)579-585
Number of pages7
JournalPolish Journal of Pharmacology
Volume46
Issue number6
StatePublished - 1994
Externally publishedYes

Keywords

  • N(G)-nitro-L-arginine methyl ester (L-NAME)
  • cyclooxygenase
  • indomethacin
  • nitric oxide synthases
  • pressure-flow curves

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Sprague, R. S., Stephenson, A. H., Dimmitt, R. A., Weintraub, N. L., Branch, C. A., McMurdo, L., & Lonigro, A. J. (1994). Inhibition of nitric oxide synthesis results in a selective increase in arterial resistance in rabbit lungs. Polish Journal of Pharmacology, 46(6), 579-585.