EFFECTS OF NITRIC-OXIDE SYNTHASE INHIBITOR ON HEMODYNAMIC CHANGE AND O-2 DELIVERY IN SEPTIC DOGS

To elucidate the role of nitric oxide (NO) in septic shock, we measure d hemodynamic and pulmonary gas changes in anesthetized dogs after int ravenous administration of bacterial lipopolysaccharide (LPS) with or without NO synthase inhibitor, N-G-nitro-L-arginine (L-NNA). Infusion of LPS (250 ng . kg(-1). min(-1)) for 2 h decreased mean arterial pres sure over 1-4 h. Although L-NNA (10 mg/kg) blocked LPS-induced hypoten sion, it decreased cardiac index, oxygen delivery index, arterial pH, and arterial Po, and increased systemic vascular resistance index in t he presence or absence of LPS. Administration of N-G-nitro-D-arginine (D-NNA, 10 mg/kg) alone caused fewer hemodynamic effects (increased sy stemic vascular resistance index and decreased cardiac index) than L-N NA alone. Our study provides evidence that L-NNA prevents endotoxin-in duced hypotension but decreases cardiac output and oxygen delivery, ef fects that may, in part, be due to a nonspecific NO synthase-independe nt event. Thus clinical use of NO synthase inhibitors for the treatmen t of septic shock should be cautiously considered.