Bradykinin actively modulates pulmonary vascular pressure-cardiac index relationships

Abstract

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 beta-adrenergic and -cholinergic receptors. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by step-wise constriction of the thoracic inferior vena cava to reduce Q. In intact dogs, bradykinin (2 micrograms X kg-1 X min-1 iv) caused systemic vasodilation, i.e., systemic arterial pressure was slightly decreased (P less than 0.05), Q was markedly increased (P less than 0.01), and mixed venous PO2 and oxygen saturation (SO2) were increased (P less than 0.01). Bradykinin decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) over the entire range of Q studied (140-60 ml X min-1 X kg-1) in intact dogs. During cyclooxygenase pathway inhibition with indomethacin, bradykinin again decreased (P less than 0.05) pulmonary arterial pressure-pulmonary capillary wedge pressure at every level of Q, although the magnitude of the vasodilator response was diminished at lower levels of Q (60 ml X min-1 X kg-1). Following combined administration of sympathetic beta-adrenergic and -cholinergic receptor antagonists, bradykinin still decreased (P less than 0.01) pulmonary arterial pressure-pulmonary capillary wedge pressure over the range of Q from 160 to 60 ml X min-1 X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulatory pathways for the stimulation of canine tracheal ciliary beat frequency by bradykinin.

“…The stimulation of vagal C fibres (Kaufman et al 1980) (Roberts, Kaufman, Baker, Braun, Coleridge & Coleridge, 1981) by intra-arterially administered bradykinin was found to be independent of cyclooxygenase pathways in dogs (Kaufman et al 1980). Also, pulmonary vasodilatation by bradykinin has also been shown to be independent of cyclooxygenase, cholinergic or adrenergic pathways (Nyhan, Clougherty, Goll & Murray, 1987). However, bradykinin has been shown to stimulate ion transport in excised tracheal epithelial tissue by a mechanism consistent with the co-release of PGE2 and independent of neural mechanisms (Leikauf et al 1985).…”

Selective endothelial dysfunction in conscious dogs after cardiopulmonary bypass

“…Endothelial-dependent hyperpolarizing factor (EDHF) may also contribute to acetylcholine-induced pulmonary vasodilation (6). Whereas the contributions of EDRF-NO, vasodilator prostaglandins (16), and EDHF in bradykinin-induced pulmonary vasodilation are well established in other models, this response appears to be primarily mediated by EDRF-NO in conscious dogs, (20) with only a minor role for vasodilator prostaglandins (24). Thus a differential pattern of endothelial mediator release in response to acetylcholine (EDRF-NO, EDHF) and bradykinin (EDRF-NO) could be an explanation for the contrasting responses observed post-CPB.…”