Inhibition of Nitric Oxide Synthase with Amino-guanidine Decrease the Systemic Inflammatory Response Following Hemorrhagic Shock in Rats

Abstract

Background: Hemorrhagic shock and resuscitation activates inflammatory cascade that involve the up regulation of cytokine synthesis. This process is associated with organ damage and death. Inducible nitric oxide synthase (iNOS) is increased during hemorrhagic shock and participate in pro-inflammatory signaling. Objectives: The aim of the present study was to examine the protective effects of inhibition of inducible nitric oxide synthase (iNOS) using Amino-guanidine against systemic inflammatory response in a rat model of hemorrhagic shock. Methods: Male Sprague- Dawley rats were assigned to 3 experimental groups (n = 6 per group): Normotensive rats (N); Hemorrhagic shock rats (HS); and Hemorrhagic shock rats treated with AG (HSAG). After 60 min hemorrhagic shock, rats were treated or not by injection of 1ml of 60 mg/Kg Amino-guanidine (AG) intra-arterially. Rats were then resuscitated in vivo by reinfusion of the shed blood to restore norm tension. The mean arterial blood pressure was monitored. Blood was collected following 60 min hemorrhage and 30 min in vivo treatment and resuscitation for TNF-a measurement. Results: The present study showed that inhibition of inducible nitric oxide synthase (iNOS) using Aminoguanidine decreased the levels of tumor necrosis factor α (TNF-α) in the plasma after one hour of hemorrhagic shock and resuscitation in rats. The results showed that hemorrhagic shock and resuscitation significantly increased the levels of TNF-α. Conclusion: Inducible nitric oxide synthase (iNOS is involved in the up regulation of the inflammatory response in resuscitated hemorrhagic shock. Inhibition of inducible nitric oxide synthase (iNOS) using Amino-guanidine (AG) reduced the inflammatory response to hemorrhagic.