Endothelin receptor blockade decreases lung water in young rats exposed to viral infection and hypoxia.
Viral respiratory infections may increase the susceptibility of young animals to hypoxia-induced pulmonary edema. Because hypoxia stimulates endothelin production, we hypothesized that an increase in lung endothelin contributes to these alterations in lung water. Weanling rats were infected with Sendai virus, causing a mild respiratory infection. At day 7 after infection, animals were exposed to hypoxia (inspired O(2) fraction = 0.1) for 24 h. Exposure to virus plus hypoxia led to increases in lung water compared with control groups (P < 0.001). Lung endothelin levels were significantly higher in the virus plus hypoxia group than in control groups (P < 0.001). A second group of infected animals received bosentan, a nonselective endothelin receptor antagonist, during exposure to hypoxia. Bosentan-treated animals showed less lung water accumulation, less lung lavage fluid protein, and less perivascular fluid cuffing than untreated animals (P < 0.01). We conclude that the combination of a recent viral respiratory infection and exposure to moderate hypoxia led to increases in endothelin in the lungs of young rats and that endothelin receptor blockade ameliorates the hypoxia-induced increases in lung water found in these animals.
Carpenter
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TC
Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. todd.carpenter@uchsc.edu
Stenmark
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KR
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D001834:Body Water / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008666:Metalloendopeptidases; D011498:Protein Precursors / Q000235:genetics; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012141:Respiratory Tract Infections / Q000378:metabolism* / Q000821:virology; D018108:Respirovirus; D010253:Respirovirus Infections / Q000378:metabolism*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes