Bradykinin actively modulates pulmonary vascular pressure-cardiac index relationships

Our objectives were to investigate the pulmonary vascular effects of exogenously administered bradykinin at normal and reduced levels of cardiac index in intact conscious dogs and to assess the extent to which the pulmonary vascular response to bradykinin is the result of either cyclooxygenase pathway activation or reflex activation of sympathetic β-adrenergic and -cholinergic receptors. 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. In intact dogs, bradykinin (2 μg·kg^-1·min^-1 iv) caused systemic vasodilation, i.e., systemic arterial pressure was slightly decreased (P < 0.05), Q̇ was markedly increased (P < 0.01), and mixed venous PO₂ and oxygen saturation (SO₂) were increased (P = 0.01). Bradykinin decreased (P < 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) over the entire range of Q̇ studied (140-60 ml·min^-1·kg^-1) in intact dogs. During cyclooxygenase pathway inhibition with indomethacin, bradykinin again decreased (P < 0.05) pulmonary arterial pressure-pulmonary capillary wedge pressure at every level of Q̇, although the magnitude of the vasodilator response was diminished at lower levels of Q̇ (160 ml·min^-1·kg^-1). Following combined administration of sympathetic β-adrenergic and -cholinergic receptor antagonists, bradykinin still decreased (P < 0.01) pulmonary arterial pressure-pulmonary capillary wedge pressure over the range of Q̇ from 160 to 60 ml·min^-1·kg^-1. Thus exogenous administration of bradykinin causes active, nonflow dependent pulmonary vasodilation over a broad range of Q̇ in intact conscious dogs. This pulmonary vasodilator response is not dependent on cyclooxygenase pathway activation or on reflex activation of β-adrenergic or -cholinergic receptors.