Pentoxifylline treatment attenuates pulmonary vasomotor dysfunction in acute lung injury.
Acute lung injury (ALI) is characterized by pulmonary hypertension. Although the pathophysiology of ALI is complex, cytokine production, especially tumor necrosis factor-alpha (TNF-alpha), is known to mediate histologic lung injury. Pentoxifylline (PTX) is known to inhibit the expression of many cytokines, including TNF-alpha. The purpose of this study was to determine the effect of PTX treatment on endotoxin-induced impairment of endothelium-dependent mechanisms of pulmonary vasorelaxation. Mechanisms of endothelium-dependent relaxation were studied with the muscarinic receptor agonist, acetylcholine (ACh), and the receptor-independent calcium ionophore, A23187. Endothelium-independent pulmonary vasorelaxation was examined by direct stimulation of smooth muscle guanylate cyclase with the nitric oxide donor, sodium nitroprusside (SNP). Five rats received PTX (50 mg/kg) and endotoxin (20 mg/kg), endotoxin alone, or saline ip. After 6 hr, dose-response curves to ACh, A23187, and SNP were determined in isolated pulmonary artery rings preconstricted with phenylephrine (PE). PTX attenuated but did not eliminate endotoxin-induced impairment of endothelium-dependent and -independent pulmonary vasorelaxation. These data suggest that PTX may offer a therapeutic modality for the treatment of pulmonary hypertension in ALI.
Sheridan
B C
BC
Department of Surgery, University of Colorado, Denver, Colorado, USA.
McIntyre
R C
RC
Meldrum
D R
DR
Fullerton
D A
DA
D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D004731:Endotoxins / Q000633:toxicity; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D004731:Endotoxins; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009599:Nitroprusside; D010431:Pentoxifylline