Influence of selective nitric oxide synthetase inhibitor for treatment of refractory haemorrhagic shock.

Abstract

Haemorrhagic shock (HS) is implicated in the induction of inducible nitric oxide synthase that leads to increased production of nitric oxide (NO). We investigated the influence of aminoguanidine (AG), a selective iNOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor and S-Nitroso-N-acetylpenicillamine (SNAP), a NO donor, each of which was given with (+) or without (-) angiotensin II (ANGII), a vasoconstrictor, on the survival rate of HS decompensatory phased (HSDP) rats. HSDP was achieved via a constant pressure method. Organs were harvested and analyzed from rats sacrificed 72 h after HSDP or upon death. Plasma collected from HSDP rats were used to measure nitrate/nitrite, GOT and creatinine levels. AG+ANGII-treated rats had significantly higher survival rates compared to the other treatment groups, 72 h following HSDP. A marked increase in MABP level was observed in AG+ANGII-treated rats when compared to other treatment groups. Histological examinations also showed a reduction of organ damage in AG+ANGII-treated rats compared to other treatment groups. Nitrate/nitrite level, glutamic oxalacetic transaminase (GOT) level and creatinine level were also significantly improved in AG+ANGII-treated rats compared to the other groups. A greater beneficial effect was achieved with treatment by the AG+ANGII combination. Our experiments showed that the inhibition of excessive NO formation that occurred during HSDP, had augmented the vascular responsiveness effect of ANGII following protracted HS.