Effects of L-arginine and L-nitro-arginine treatment on blood pressure and cardiac output in a rabbit endotoxin shock model

OBJECTIVE: To verify the effect of nitric oxide system modification during sepsis, not only in terms of pressure but also in terms of perfusion flow. DESIGN: Experimental, comparative study. SETTING: Laboratory of a university hospital. SUBJECTS: Twenty-six New Zealand male rabbits (2 to 2.5 kg body weight) were studied under anesthesia. INTERVENTIONS: Nitric oxide pathways were modified during shock-induced hypotension, using L-arginine (600 mg/kg) and L-nitro-arginine (7.5 mg/kg), which were infused 75 mins after endotoxin injection. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure (MAP) and cardiac output, as well as ascending aortic velocity, were measured and aortic conductance (aortic velocity/MAP in cm/sec/mm Hg) was calculated. Both L-arginine and L-nitro-arginine increased MAP to the pre-endotoxin level, but only L-arginine increased aortic velocity in association with a marked increase in aortic conductance (p < .001). L-nitro-arginine significantly (p < .05) decreased aortic velocity as compared with the control endotoxin group, with an intense vasoconstriction as shown by a significant (p < .001) decrease in aortic conductance. CONCLUSIONS: These results, along with the high mortality rate in the L-nitro-arginine treated group, challenge the hypothesis that nitric oxide release inhibition has a beneficial effect in septic shock.