Endotoxin-induced acute lung injury is enhanced in rats with spontaneous hypertension

摘要: SUMMARY 1 Acute lung injury (ALI), or acute respiratory distress syndrome, is a major cause of mortality in endotoxaemia. The present study tested whether the endotoxaemia-induced changes and associated ALI were enhanced rats with established hypertension to examine possible mechanisms involved. 2 Fifty spontaneously hypertensive (SHR) same number normotensive Wistar Kyoto (WKY) rats, aged 12–15 weeks, used. experiments performed conscious, unanaesthetized rats. Endotoxaemia was produced by intravenous lipopolysaccharide (LPS; 10 mg/kg). NG-Nitro-l-arginine methyl ester (l-NAME; 10 mg/kg, i.v.), l-N6-(1-iminoethyl)-lysine (l-Nil; 5 mg/kg, i.v.) 3-morpholinosydnonimine (SIN-1; given 5 min before LPS observe effects nitric oxide synthase (NOS) inhibition (NO) donation. 3 We monitored arterial pressure heart rate evaluated determining weight/bodyweight ratio, weight gain, leakage Evans blue dye, protein concentration bronchoalveolar lavage histopathological examination. Plasma nitrate/nitrite, guanidine, pro-inflammatory cytokines, including tumour necrosis factor-α interleukin-1β, tissue cGMP determined. Expression mRNA for inducible endothelial NOS examined using reverse transcription–polymerase chain reaction. 4 Lipopolysaccharide caused systemic hypotension, increases plasma cytokines content. LPS-induced greater SHR than WKY Pretreatment l-NAME l-Nil attenuated, whereas NO donor SIN-1 aggravated, endotoxin-induced changes. 5 In conclusion, genetic are more susceptible endotoxaemia this results extent compared