Role of nitric oxide in the regulation of glucose kinetics in response to endotoxin in dogs

The purpose of the present in vivo study was to determine the role of nitri c oxide (NO) in the regulation of glucose metabolism in response to endotox in by blocking NO synthesis with N-G-monomethyl-L-arginine (L-NMMA). In fiv e dogs, the appearance and disappearance rates of glucose (by infusion of [ 6,6-H-2(2)] glucose), plasma glucose concentration, and plasma hormone conc entrations were measured on five different occasions: saline infusion, endo toxin alone (E coli, 1.0 mug/kg iv), and endotoxin administration plus thre e different doses of primed, continuous infusion of L-NMMA. Endotoxin incre ased rate of appearance of glucose from 13.7 +/- 1.6 to 23.6 +/- 3.3 mu mol .kg(-1).min(-1) (P < 0.05), rate of disappearance of glucose from 13.9 <plu s/minus> 1.1 to 24.8 +/- 3.1 mu mol.kg(-1).min(-1) (P < 0.001), plasma lact ate from 0.5 <plus/minus> 0.1 to 1.7 +/- 0.1 mmol/l (P < 0.01), and counter regulatory hormone concentrations. L-NMMA did not affect the rise in rate o f appearance and disappearance of glucose, plasma lactate, or the counterre gulatory hormone response to endoxin. Plasma glucose levels were not affect ed by endotoxin with or without L-NMMA. In conclusion, in vivo inhibition o f NO synthesis by high doses of L-NMMA does not affect glucose metabolism i n response to endotoxin, indicating that NO is not a major mediator of gluc ose metabolism during endotoxemia in dogs.