Arachidonic acid and pulmonary function in heart-lung-preparation of guinea-pig: modulation by PCO2.
In normocapnic and deeply hypocapnic guinea-pig heart-lung-preparations (HLPs), dose-response relationships were estimated for the bronchoconstrictor and pulmonary hypertensive responses to histamine (H), 5 hydroxytryptamine (5HT), arachidonic acid (AA) and U-46619, a prostaglandin endoperoxide analogue acting on thromboxane (TXA2) receptors. Hypocapnia potentiated in a different way the bronchoconstrictor effects of AA (increased slope of dose-response curve) and of U-46619 (shift to the left of the curve). The pulmonary vascular effects of U-46619 were unaffected by CO2 tension, whereas a linear log dose-dependence of the pulmonary hypertensive responses to AA was present only in hypocapnic HLPs. The amount of TXA2-like material released in normocapnic HLPs was compatible with the AA/U-46619 potency ratio calculated for the bronchoconstrictor responses in normocapnic HLPs and for the pulmonary vascular responses in hypocapnic HLPs. The above described effects of hypocapnia were different from those produced on the bronchial and pulmonary vascular reactivity to H and 5HT, suggesting that specific mechanisms are involved in the modulating effect of PCO2. The inhibition by indomethacin of AA-induced pulmonary vasoconstriction was unaffected by changes in CO2 tension; conversely, the bronchoconstrictor effects of AA were more substantially reduced by indomethacin in normocapnic HLPs. It is concluded that: the relative contribution of different AA metabolites to the final response of the airway system to the precursor is affected by changes in CO2 tension; different receptorial or prereceptorial mechanisms are involved in the CO2-AA interaction taking place in the two components of the lung parenchyma; the pulmonary outflow of AA metabolites provides only circumstantial evidence of the functional meaning of this release.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000502:physiology*; D002245:Carbon Dioxide / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D001095:Arachidonic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D002245:Carbon Dioxide; D016718:Arachidonic Acid; D012701:Serotonin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D006632:Histamine; D007213:Indomethacin