The effect of indomethacin on plasma and lung lymph angiotensin converting enzyme activity in sheep

The effect of indomethacin (INDO), an inhibitor of prostaglandin (PG) cyclooxygenase, on pulmonary vascular permeability is unclear. We measured angiotensin converting enzyme (ACE) activity in plasma and lung lymph in order to evaluate pulmonary endothelial integrity. Eighteen sheep, anesthetized and acutely prepared for the collection lung lymph, were used in the study. Four animals (Group I) served as sham controls and were not subjected to experimental intervention. In order to minimize changes in pulmonary microvascular surface area (PMSA), left atrial blood pressure (Pla) was elevated (12-20 Torr) following the baseline period in animals in the three experimental groups. Group II (n = 4) was subjected to increased Pla only in order to assess the effects of that maneuver alone on experimental parameters. Group III (n = 3) received an infusion of buffered vehicle only during a four hour period of elevated Pla, and, thus served as a vehicle control for Group IV (n = 7) which received INDO for the same period of increased Pla. Pulmonary blood pressures, cardiac output (CO), lung lymph flow (Ql) and the ratio of lymph to plasma protein concentration (L/P) were measured in all experiments in order to independently assess changes in lung vascular permeability. While ACE activity in plasma and lymph fell in each experimental group, average ACE experimental values were unchanged from corresponding baseline values. Increased Pla caused a characteristic increase in Ql and fall in L/P in each of the experimental groups. We conclude that INDO does not alter lung fluid and protein balance by a process which involves increased pulmonary vascular permeability secondary to a loss of endothelial integrity.