Pulmonary vascular alpha 1-adrenoreceptor activity in conscious dogs after left lung autotransplantation

We investigated the extent to which sympathetic alpha 1-adrenoreceptor activation is involved in chronic pulmonary vascular regulation in conscious dogs after left lung autotransplantation (LLA). Continuous left pulmonary vascular pressure-flow plots were generated in conscious dogs 3–4 wk post-LLA and in identically instrumented conscious dogs not subjected to LLA (sham-operated controls). LLA resulted in a marked upward shift in the baseline left pulmonary vascular pressure-flow relationship compared with the control group (P < 0.01), i.e., LLA caused a chronic increase in pulmonary vascular resistance. The sympathetic alpha 1-adrenoreceptor antagonist prazosin partially reversed (P < 0.01) the LLA-induced increase in pulmonary vascular resistance. Circulating concentrations of norepinephrine and epinephrine at 2 and 4 wk post-LLA were not significantly different from values measured in control dogs. However, the dose-response relationship to the exogenous administration of the sympathetic alpha 1-adrenoreceptor agonist phenylephrine was shifted (P < 0.05) to the left post-LLA compared with control, which indicates an increase in pulmonary vascular reactivity to alpha 1-adrenoreceptor activation. This effect was not due to a generalized increase in pulmonary vascular reactivity to vasoconstrictor stimuli because the dose-response relationship to the thromboxane analogue U-46619 was not significantly altered post-LLA compared with control. Thus LLA results in a chronic increase in pulmonary vascular resistance in conscious dogs. A component of the increase in pulmonary vascular resistance resulting from LLA is mediated by an enhanced reactivity to sympathetic alpha 1-adrenoreceptor activation.