PENTOXIFYLLINE TREATMENT ATTENUATES PULMONARY VASOMOTOR DYSFUNCTION IN ACUTE LUNG INJURY

Acute lung injury (ALI) is characterized by pulmonary hypertension, Al though the pathophysiology of ALI is complex, cytokine production, esp ecially tumor necrosis factor-alpha (TNF-alpha), is known to mediate h istologic lung injury, Pentoxifylline (PTX) is known to inhibit the ex pression of many cytokines, including TNF-alpha. The purpose of this s tudy was to determine the effect of PTX treatment on endotoxin-induced impairment of endothelium-dependent mechanisms of pulmonary vasorelax ation, Mechanisms of endothelium-dependent relaxation were studied wit h the muscarinic receptor agonist, acetylcholine (ACh), and the recept or-independent calcium ionophore, A23187. Endothelium-independent pulm onary vasorelaxation was examined by direct stimulation of smooth musc le guanylate cyclase with the nitric oxide donor, sodium nitroprusside (SNP). Five rats received PTX (50 mg/kg) and endotoxin (20 mg/kg), en dotoxin alone, or saline ip, After 6 hr, dose-response curves to ACh, A23187, and SNP were determined in isolated pulmonary artery rings pre constricted with phenylephrine (PE), PTX attenuated but did not elimin ate endotoxin-induced impairment of endothelium-dependent and -indepen dent pulmonary vasorexaxation. These data sup suggest that PTX may off er a therapeutic modality for the treatment of pulmonary hypertension in ALL. (C) 1997 Academic Press.