In vivo measurement of nitric oxide production in porcine gut, liver and muscle during hyperdynamic endotoxaemia

In vivo measurement of nitric oxide production in porcine gut, liver and muscle during hyperdynamic endotoxaemia.Bruins MJ, Lamers WH, Meijer AJ, Soeters PB, Deutz NE.Department of Surgery, Maastricht University, Maastricht, The Netherlands. Department of Anatomy & Embryology University of Amsterdam, AMC, The Netherlands. Department of Biochemistry, University of Amsterdam, AMC, The Netherlands.1 During prolonged endotoxaemia, an increase in arginine catabolism may result in limiting substrate availability for nitric oxide (NO) production. These effects were quantitated in a chronically instrumented porcine endotoxaemia model. 2 Ten days prior to the beginning of the experiments, pigs were catheterized. On day 0, pigs received a continuous infusion of endotoxin (3 micro g kg(-1) h(-1)) over 24 h and were saline resuscitated. Blood was drawn from the catheters at 0 and 24 h during primed-infusion of (15)N(2)-arginine and P-aminohippurate to assess (15)N(2)-arginine to (15)N-citrulline conversion and plasma flow rates, respectively, across the portal-drained viscera, liver and hindquarter. 3 During endotoxin infusion a hyperdynamic circulation with elevated heart rate, cardiac index and decreased mean arterial pressure was achieved, characteristic of the human septic condition. 4 Endotoxin induced NO production by the portal-drained viscera and the liver. The increased NO production was quantitatively matched by an increase in arginine disposal. Nitrite/nitrate levels remained unchanged during endotoxaemia. 5 Despite an increased arginine production from the hindquarter and an increased whole-body arginine appearance rate during endotoxin infusion, the plasma arginine concentration was lower in endotoxin-treated animals than in controls. 6 On a whole-body level, the muscle was found to serve as a major arginine supplier and, considering the lowered arginine plasma levels, seems critical in providing arginine as precursor for NO synthesis in the splanchnic region. British Journal of Pharmacology (2002) 137, 1225-1236. doi:10.1038/sj.bjp.0704993