Pulmonary vascular responses to angiotensin II and captopril in conscious dogs

Our objectives were to investigate the extent to which angiotensin II (ANG II) and converting-enzyme inhibition (CEI) exert a direct vasoactive influence on the pulmonary circulation of conscious dogs. Multipoint pulmonary vascular pressure-cardiac index (P/Q̇) plots were constructed during normoxia in conscious dogs by stepwise constriction of the thoracic inferior vena cava to reduce Q̇. The effects of ANG II infusion (60 ng·kg^-1·min^-1, iv) and CEI with captopril (1 mg/kg plus 1 mg·kg^-1·h^-1, iv) on pulmonary vascular P/Q̇ plots were assessed first with the conscious dogs intact and again after combined administration of pharmacological antagonists to block sympathetic α- and β-adrenergic, cholinergic, and arginine vasopressin receptors. In intact dogs, ANG II increased (P < 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure, PAP-PCWP) over the entire range of Q̇ studied (60-120 ml·min^-1·kg^-1). Conversely, CEI decreased (P < 0.05) PAP-PCWP at each level of Q̇. After administration of the autonomic nervous system and arginine vasopressin receptor antagonists, ANG II again increased (P < 0.01) and CEI decreased (P < 0.01) PAP-PCWP over the entire range of Q̇ studied. Thus exogenous administration of ANG II results in active, nonflow-dependent constriction of the pulmonary circulation, and this effect is not dependent on the autonomic nervous system or increased circulating levels of arginine vasopressin. Moreover, the active, nonflow-dependent vasodilation observed during CEI before and after neurohumoral block supports the concept that endogenous ANG II exerts a vasoconstrictor influence on the pulmonary circulation over a broad range of cardiac index in conscious dogs.