Pulmonary vascular beta-adrenoreceptor activity in conscious dogs after left lung autotransplantation

Abstract

Our objective was to determine whether chronic denervation associated with left lung autotransplantation (LLA) results in an alteration in sympathetic beta-adrenoreceptor regulation of the pulmonary circulation in conscious dogs. Continuous left pulmonary vascular pressure-flow (LPQ) plots were generated in conscious dogs 2-4 wk post-LLA and in sham-operated control conscious dogs. We tested the hypothesis that endogenous sympathetic beta-adrenoreceptor activation via circulating catecholamines acted to attenuate the chronic increase in pulmonary vascular resistance post-LLA. Administration of the sympathetic beta-adrenoreceptor antagonist propranolol had no significant effect on the LPQ relationship post-LLA. We also tested the hypothesis that pulmonary vascular reactivity to sympathetic beta-adrenoreceptor activation would be increased post-LLA. The thromboxane analogue U-46619 was used to acutely preconstrict (P < 0.01) the pulmonary circulation in control dogs; this preconstriction shifted the LPQ relationship to the same position measured post-LLA. Under these conditions, cumulative doses of the beta-adrenoreceptor agonist isoproterenol caused pulmonary vasodilation (P < 0.01) in the control group but had no effect post-LLA. However, after acute preconstriction with U-46619, the pulmonary vasodilator response (P < 0.01) to isoproterenol post-LLA was not significantly different from that in the control group. These differential responses to isoproterenol with and without acute preconstriction indicate that a significant component of the chronic increase in pulmonary vascular resistance post-LLA is mediated by passive nonvasoactive mechanisms. Moreover, sympathetic beta-adrenoreceptor reactivity of the pulmonary circulation is not enhanced by chronic denervation resulting from the LLA procedure.