title: In vivo arginine production and intravascular nitric oxide synthesis in hypotensive sepsis.
abstract: BACKGROUND
  Arginine is important in the response to infections and is a precursor for the synthesis of the vasodilator nitric oxide (NO). Low plasma arginine is correlated with a worse prognosis in patients with sepsis, and increased NO has been implicated in the hypotension of sepsis. Data on in vivo arginine and NO kinetics are lacking in hypotensive septic adults.
  
  
  OBJECTIVE
  We aimed to measure in vivo arginine production and the intravascular NO synthesis rate in hypotensive septic patients.
  
  
  METHODS
  Arginine flux and the fractional and absolute synthesis rates of plasma NO were measured in fasted healthy (n = 10) and hypotensive septic (n = 6) adults by using a 6-h constant infusion of [15N2-guanidino]arginine. Urinary excretion of the NO metabolites nitrite and nitrate (NOx) and plasma concentrations of NOx, arginine, and creatinine were also measured.
  
  
  RESULTS
  All patients had hyperdynamic septic shock and impaired renal function. Compared with the control subjects, the patients had slower arginine flux (99 +/- 8 compared with 50 +/- 7 micromol x kg(-1) x h(-1); P < 0.01), lower plasma arginine concentrations (75 +/- 8 compared with 40 +/- 11 micromol/L; P < 0.01), higher plasma NOx concentrations (30 +/- 4 compared with 65 +/- 1.8 micromol/L), and a slower fractional synthesis rate of NOx. There was no significant difference in the absolute synthesis rate of NOx between groups. In patients with sepsis, the plasma NOx concentration correlated with the glomerular filtration rate and plasma creatinine but not with mean arterial pressure.
  
  
  CONCLUSIONS
  Patients with septic shock have a shortage in the availability of arginine associated with a slower production. Impaired renal excretion of NOx is a contributor to the high plasma NOx in these patients.
authors.affiliation: US Department of Agriculture, Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, and Medical Services, Ben Taub General Hospital, Houston, TX, USA.
authors.forename: Salvador
authors.initials: S
authors.lastname: Villalpando
authors.forename: Jayashree
authors.initials: J
authors.lastname: Gopal
authors.forename: Ashok
authors.initials: A
authors.lastname: Balasubramanyam
authors.forename: Venkata P
authors.initials: VP
authors.lastname: Bandi
authors.forename: Kalpalatha
authors.initials: K
authors.lastname: Guntupalli
authors.forename: Farook
authors.initials: F
authors.lastname: Jahoor
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000096:biosynthesis*; D016022:Case-Control Studies; D016638:Critical Illness; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007022:Hypotension / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000097:blood; D009587:Nitrogen Isotopes; D012772:Shock, Septic / Q000378:metabolism*
chemical_list: D009566:Nitrates; D009573:Nitrites; D009587:Nitrogen Isotopes; D009569:Nitric Oxide; D001120:Arginine