Bradykinin-induced increase in pulmonary vascular permeability in hypoxic sheep

Bradykinin (BK) is a potent edematogenic agent in systemic tissues. It is degraded by angiotensin-converting enzyme (ACE), which is located on the surface of all vascular endothelia. We hypothesized that since oxygen tension modulates ACE activity, the high pulmonary oxygen tension and hence high ACE activity protects the lung from the edematogenic effects of BK. We therefore studied the effect of exogenous BK in unanesthetized sheep with surgically created lymph fistulas and vascular catheters during normoxia and hypoxia. BK significantly elevated lung lymph flow and protein flux only when the sheep were made hypoxic and the lung's ability to degrade BK was impaired. This increase could not be attributed to recruitment of vascular surface area or to an increase in the driving force for fluid exchange because there were no changes in pulmonary arterial or left atrial pressures, cardiac output, or pulmonary vascular resistance. We conclude that BK increases water and protein movement in the lung by increasing vascular permeability.