Nitric oxide and the haemodynamic profile of endotoxin shock in the conscious mouse

British Journal of Pharmacology
D D ReesS Moncada

Abstract

1. The release of cytokines following administration of endotoxin and the contribution of nitric oxide (NO) to the subsequent haemodynamic profile were investigated in the conscious mouse. 2. Administration of endotoxin (E. Coli, 026:B6, 12.5 mg kg(-1), i.v.) elevated the concentration of tumour necrosis factor-alpha (TNF-alpha) in the plasma within 0.5 h, reaching a maximum at 2 h and returning to control concentrations by 4 h. In addition, the concentration of interleukin-6 (IL-6) in the plasma was also elevated within 1 h, reaching a maximum at 3 h and remaining elevated throughout the 12 h of study. 3. Endotoxin (12.5 mg kg(-1), i.v.) induced the expression of a Ca2+-independent (inducible) NO synthase in the mouse heart and elevated the concentrations of nitrite and nitrate in the plasma within 4 h, reaching a maximum at 12 h. This was accompanied by a progressive fall in blood pressure over the same period. 4. The vasopressor effect of noradrenaline (0.5-4 microg kg(-1) min(-1), i.v.) administered as a continuous infusion was significantly attenuated 7 h after endotoxin (12.5 mg kg(-1), i.v). 5. The NO synthase inhibitor NG-monomethyl-L-arginine HCl (L-NMMA; 1-10 mg kg(-1), i.v. bolus) reversed the fall in blood pressure ...Continue Reading

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