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

• Published in: Resuscitation 2004-05, Vol.61 (2), p.221-229
• Main Authors: Shirhan, Md, Moochhala, Shabbir M., Kerwin, Siew-Yang Low, Ng, Kian Chye, Lu, Jia
• Format: Article
• Language: English
• Subjects: Aminoguanidina; Aminoguanidine; Analysis of Variance; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Angiotensin II - pharmacology; Animals; Biological and medical sciences; Biomarkers - analysis; Blood Pressure Determination; Choque hemorrágico; Creatinine - metabolism; Guanidines - pharmacology; Haemorrhagic shock; Intensive care medicine; Male; Medical sciences; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Oxido nı́trico; Probability; Random Allocation; Rat; rata; Ratos; Rats; Rats, Sprague-Dawley; Sensitivity and Specificity; Shock, Hemorrhagic - drug therapy; Shock, Hemorrhagic - mortality; Shock, Hemorrhagic - pathology; SOC hemorrágico; Survival Rate
• ISSN: 0300-9572; 1873-1570
• DOI: 10.1016/j.resuscitation.2004.01.005

Objective: 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. Materials and methods: 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. Results: 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. Conclusions: 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. Objectivo: O choque hemorrágico (HS) está implicado na indução da sı́ntese inductı́vel do óxido nı́trico que leva a elevação da produção do óxido nı́trico (NO). Investigámos a influência da aminoguanidina (AG), um inibidor selectivo da iNOS, N G-nitro- l-arginina metil Ester ( l-NAME), e de um inibidor não selectivo e S-Nitroso- N-acetilpenicilamina (SNAP), um fornecedor de NO, cada um dos quais foi administrado com (+) ou sem (−) angiotensina II (ANGII), um vasoconstritor, na taxa de sobrevivência da fase descompensada do HS (HSDP) em ratos. Material e métodos: Foi obtido HSDP através de um método de pressão constante. Foram recolhidos e analisados os órgãos de ratos sacrificados 72 h após HSDP ou após morte. Foram realizadas medições de nı́veis de nitrato/nitrito, GOT e creatinina do plasma colhido de ratos HSDP. Resultados: 72 h após HSDP os ratos tratados com AG + ANGII tiveram ta