NITRIC-OXIDE AS A MEDIATOR OF REDUCED ARTERIAL RESPONSIVENESS IN SEPTIC PATIENTS

Objective: To investigate the functional status of arteries in patient s with septic shock, each of whom suffered from severe hypotension. De sign: Experimental, comparative study. Setting: Laboratory in a univer sity hospital. Subjects: Mesenteric artery resected from omentum was o btained from patients (n = 3) with or without (n = 4) sepsis. Interven tions: To study the effect of modification of the nitric oxide system in human arteries during sepsis, changes in norepinephrine evoked isom etric tension in mesenteric arterial rings were measured. Measurements and Main Results: Mesenteric arteries were isolated from omentum rese cted from three patients with septic shock and from four patients with no inflammatory conditions; in each case, during an intestinal anasto mosis, In arterial rings, after a l-hr equilibration with Krebs soluti on, changes in isometric tension evoked by norepinephrine were measure d 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 mu mol/L of N-G-nitro-L-arginine methyl ester or 10 mu mol/L of methylene blue reversed this decrease. Conclusion: These res ults indicate that in patients with septic shack, the main cause of re duced sensitivity to presser agents may be a massive generation of nit ric oxide via the L-arginine pathway.