Nitric oxide as a mediator of reduced arterial responsiveness in septic patients.
OBJECTIVE
To investigate the functional status of arteries in patients with septic shock, each of whom suffered from severe hypotension.


METHODS
Experimental, comparative study.


METHODS
Laboratory in a university hospital.


METHODS
Mesenteric artery resected from omentum was obtained from patients (n = 3) with or without (n = 4) sepsis.


METHODS
To study the effect of modification of the nitric oxide system in human arteries during sepsis, changes in norepinephrine-evoked isometric tension in mesenteric arterial rings were measured.


RESULTS
Mesenteric arteries were isolated from omentum resected from three patients with septic shock and from four patients with no inflammatory conditions; in each case, during an intestinal anastomosis. In arterial rings, after a 1-hr equilibration with Krebs solution, changes in isometric tension evoked by norepinephrine were measured for 5 mins every 20 mins. The tension initially evoked in rings from septic patients was lower than in those rings from nonseptic patients and, unlike the controls, it decreased with a short time course. The addition of 300 micromol/L of N(G)-nitro-L-arginine methyl ester or 10 micromol of N(G)-nitro-L-arginine methyl ester or 10 micromol/L of methylene blue reversed this decrease.


CONCLUSIONS
These results indicate that in patients with septic shock, the main cause of reduced sensitivity to pressor agents may be a massive generation of nitric oxide via the L-arginine pathway.
Tsuneyoshi
I
I
Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, Japan.
Kanmura
Y
Y
Yoshimura
N
N
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007022:Hypotension / Q000150:complications / Q000209:etiology; D008638:Mesenteric Arteries / Q000187:drug effects*; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D009638:Norepinephrine / Q000494:pharmacology*; D012772:Shock, Septic / Q000150:complications / Q000209:etiology / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine