Influence of L-arginine, aminoguanidine, and N-G-nitro-L-arginine methyl ester (L-NAME) on the survival rate in a rat model of hemorrhagic shock

Nitric oxide (NO) has been implicated in the pathophysiology of hemorrhagic shock. We investigated the influence of L-arginine (the precursor of NO sy nthesis), N-G-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG ) (inhibitors of NO synthase, with selectivity toward the constitutive and inducible isoforms, respectively) on the survival rate in a rat model of he morrhagic shock. Anesthetized, male Sprague-Dawley rats (300-350 g) were su bjected to hemorrhagic shock for 30 min followed by intravenous injection(1 mL/kg) with normal saline, L-arginine (30 mg/kg), L-NAME (10 mg/kg), L-NAM E+L-arginine, AG (1, 10, 100 mg/kg) or AG (100 mg/kg)+L-arginine (n = 5 per group). Hemorrhagic shocked rats treated with saline died within 90 min. I n contrast, L-NAME increased the survival time to >72 h in shocked rats. AG (1, 10, and 100 mg/kg) increased the survival time of shocked animals to 1 50 min, 230 min, and >72 h, respectively. Shocked rats treated with L-argin ine died within 80 min, and those that received L-NAME+L-arginine and AG+L- arginine died within 120 min and 110 min, respectively. L-NAME and AG (dose dependently) reduced macroscopic and microscopic injuries, nitrate/nitrite , PGE(2) and creatinine production, and inhibited GOT activity in shocked a nimals. L-arginine reversed the beneficial effects of AG and L-NAME, sugges ting the involvement of NO in the pathophysiology of hemorrhagic shock.