Effects of continuous infusion of nitroglycerin on pulmonary hemodynamics, lung lymph balance, and prostanoid products in the response to endotoxin in awake sheep

Abstract

We examined the effects of continuous intravenous infusion of nitroglycerin (NTG) on lung dysfunction induced by endotoxemia in awake sheep chronically instrumented with lung lymph fistula. We measured the responses of hemodynamics, lung lymph balance, and thromboxane (Tx)B₂ and 6-keto-prostaglandin (PG) Fla levels in plasma and lung lymph to endotoxin administration (1 µg/kg, intravenously [IV], over 30 min) with and without continuous infusion of NTG (1 µg/kg/min). Continuous infusion of NTG alone (n = 5) over 5 hr did not significantly alter systemic, pulmonary hemodynamics, and/or lung lymph fluid filtration. Infusion of endotoxin alone (n = 7) caused remarkable increases in pulmonary artery pressure (Ppa) and lung lymph flow (Qlym) in the early phase. Continuous infusion of NTG (n = 6) significantly prevented the early increases in Ppa and Qlym after endotoxin. The increased values of TxB₂ and 6-keto-PGF_1α in both plasma and lung lymph after endotoxemia showed the same increases in groups with and without NTG. These findings suggest that the reduction of pulmonary artery pressure induced by NTG decreased the filtration of fluid into the lungs associated with endotoxemia in sheep, and that the mechanism of vasodilating action of NTG is not due to modifications of constrictive-dilated cyclo-oxygenase products of arachidonate, such as TxA₂ and PGI₂.