Role of endothelin in endotoxin-induced sustained pulmonary hypertension in sheep

American Journal of Respiratory and Critical Care Medicine
J R SnapperW Lu

Abstract

BMS182874, an endothelin receptor antagonist, blocks the effects of exogenously administered endothelins in chronically instrumented awake sheep. A possible role for endothelin in endotoxin-induced pulmonary hypertension in sheep was investigated by studying animals given intravenous endotoxin with and without pretreatment with BMS182874. BMS182874 administration alone caused a reduction in pulmonary artery pressure (P[PA]) and systemic arterial pressure (P[SA]). Endotoxin alone caused an acute, nearly threefold increase in P(PA) which was followed, from 2-5 h after endotoxin, by a sustained but less severe increase in P(PA). These changes were accompanied by a threefold increase in lung lymph flow and dramatic increases in plasma and lung lymph thromboxane B2 concentrations. Pretreatment with BMS182874 significantly attenuated the early endotoxin-induced acute increase in P(PA) and completely blocked the late sustained pulmonary hypertension (p < 0.05), while having no affect on the increases in thromboxane levels. BMS182874 shifts the dose response curve for U46619, a prostaglandin H2 analogue, to the right. BMS182874, in addition to functioning as an endothelium receptor antagonist, appears to counteract the action of thromb...Continue Reading

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Citations

Jun 1, 2005·The Journal of Surgical Research·Christa BoerPieter Sipkema
Jun 1, 2002·Pathophysiology : the Official Journal of the International Society for Pathophysiology·Philippe R. Bauer
Feb 8, 2000·The International Journal of Biochemistry & Cell Biology·M J BoscoeM H Yacoub
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Oct 29, 2008·Critical Care : the Official Journal of the Critical Care Forum·Sebastien TrachselGöran Hedenstierna
Nov 20, 2002·Pediatric Research·Namasivayam AmbalavananYiu-Fai Chen
Dec 1, 2001·Biological & Pharmaceutical Bulletin·K Goto
Jun 22, 2010·Cardiovascular Therapeutics·Gan Hui-li
Mar 10, 2004·The Journal of Pharmacy and Pharmacology·Aarati RaiAnil Gulati
Sep 30, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Christa BoerPieter Sipkema
Jul 4, 2003·Canadian Journal of Physiology and Pharmacology·S Magder, P Cernacek
Jan 7, 2000·Anesthesia and Analgesia·P T MurrayJ G Umans

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