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• W2034789180 abstract "Endothelin‐1 is a potent mediator of sepsis‐induced pulmonary hypertension (PH). The pulmonary vascular effects of selective blockade of endothelin receptor subtype A (ET A R) during endotoxemia remain unknown. We hypothesized that selective ET A R antagonism attenuates endotoxin‐induced PH and improves pulmonary artery (PA) vasoreactivity. Adult male Sprague‐Dawley rats (250–450 g) received lipopolysaccharide (LPS; Salmonella typhimurium ; 20 mg/kg intraperitoneally) or vehicle 6 hours before hemodynamic assessment and tissue harvest. The selective ET A R antagonist sitaxsentan (10 or 20 mg/kg) or vehicle was injected intravenously 3 hours after receipt of LPS. Right ventricular systolic pressure, mean arterial pressure (MAP), cardiac output (CO), oxygenation ( P/F ratio), and serum bicarbonate were measured. Bronchoalveolar lavage (BAL) cell differential and lung wet‐to‐dry ratios were obtained. Endothelium‐dependent and endothelium‐independent vasorelaxations were determined in isolated PA rings. PA interleukin (IL)‐1β, IL‐6, tumor necrosis factor α (TNF‐α), and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) were measured. LPS caused PH, decreased MAP, CO, and serum bicarbonate, and increased PA IL‐1β, IL‐6, TNF‐α, and iNOS mRNA. Sitaxsentan attenuated sepsis‐induced PH and increased MAP. The P/F ratio, CO, serum bicarbonate, and BAL neutrophilia were not affected by sitaxsentan. In isolated PA rings, while not affecting phenylephrine‐induced vasocontraction or endothelium‐dependent relaxation, sitaxsentan dose‐dependently attenuated LPS‐induced alterations in endothelium‐independent relaxation. PA cytokine mRNA levels were not significantly attenuated by ET A R blockade. We conclude that ET A R blockade attenuates endotoxin‐induced alterations in systemic and PA pressures without negatively affecting oxygenation. This protective effect appears to be mediated not by attenuation of sepsis‐induced cardiac dysfunction, acidosis, or alveolar inflammation but rather by improved endothelium‐independent vasorelaxation." @default.
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• W2034789180 date "2014-06-01" @default.
• W2034789180 modified "2023-10-17" @default.
• W2034789180 title "Selective Endothelin‐A Receptor Blockade Attenuates Endotoxin‐Induced Pulmonary Hypertension and Pulmonary vascular dysfunction" @default.
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• W2034789180 doi "https://doi.org/10.1086/675993" @default.
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