title: In vivo measurement of nitric oxide production in porcine gut, liver and muscle during hyperdynamic endotoxaemia.
abstract: 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 microg 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.
authors.affiliation: Department of Surgery, Maastricht University, Maastricht, The Netherlands. m.bruins@chem.leidenuniv.nl
authors.forename: Maaike J
authors.initials: MJ
authors.lastname: Bruins
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Lamers
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Meijer
authors.forename: Peter B
authors.initials: PB
authors.lastname: Soeters
authors.forename: Nicolaas E P
authors.initials: NE
authors.lastname: Deutz
mesh_terms: D000818:Animals; D001120:Arginine / Q000097:blood / Q000378:metabolism; D004064:Digestive System / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D018805:Sepsis / Q000378:metabolism; D013552:Swine
chemical_list: D009569:Nitric Oxide; D001120:Arginine