title: Pentoxifylline treatment attenuates pulmonary vasomotor dysfunction in acute lung injury.
abstract: 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.
authors.affiliation: Department of Surgery, University of Colorado, Denver, Colorado, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Sheridan
authors.forename: R C
authors.initials: RC
authors.lastname: McIntyre
authors.forename: D R
authors.initials: DR
authors.lastname: Meldrum
authors.forename: D A
authors.initials: DA
authors.lastname: Fullerton
mesh_terms: 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*
chemical_list: D004731:Endotoxins; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009599:Nitroprusside; D010431:Pentoxifylline