In vivo arginine production and intravascular nitric oxide synthesis in hypotensive sepsis.
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.
Villalpando
Salvador
S
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.
Gopal
Jayashree
J
Balasubramanyam
Ashok
A
Bandi
Venkata P
VP
Guntupalli
Kalpalatha
K
Jahoor
Farook
F
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*
D009566:Nitrates; D009573:Nitrites; D009587:Nitrogen Isotopes; D009569:Nitric Oxide; D001120:Arginine