Combined neurohumoral block modulates pulmonary vascular P/Q̇ relationship in conscious dogs

Our objective was to investigate the integrated pulmonary vascular response of conscious dogs to combined inhibition of the autonomic nervous system, arginine vasopressin (V₁) receptors (vasopressinergic V₁), and converting enzyme to identify the overall influence of these three major neurohumoral mechanisms in vascular regulation of the pulmonary circulation. Multipoint pulmonary vascular pressure-cardiac index (P/Q̇) plots were generated by graded constriction of the thoracic inferior vena cava, which produced stepwise decreases in Q̇. When compared with the P/Q̇ relationship measured in intact conscious dogs, combined neurohumoral block resulted in active, nonflow-dependent pulmonary vasodilation. A second objective was to assess the extent to which cyclooxygenase pahway inhibition modified both the intact P/Q̇ relationship and the pulmonary vasodilator response to combined neurohumoral block. Cyclooxygenase inhibition alone (either indomethacin or sodium meclofenamate) resulted in active, nonflow-dependent pulmonary vasoconstriction. Moreover, the pulmonary vasodilation in response to combined neurohumoral block was entirely abolished following cyclooxygenase inhibition. Thus the integrated pulmonary vascular response to conscious dogs to combined neurohumoral block is active vasodilation. This response appears to be mediated by metabolites of the cyclooxygenase pathway.