Effect of nitric oxide scavengers, carboxy-PTIO on endotoxin induced shock in sheep

Abstract

Physiological changes associated with septic shock are due to an interplay of a number of inflammatory mediators which increase capillary permeability and vasodilation leading to circulatory disturbance. Research evidence shows that sepsis-associated vascular relaxation is mediated by nitric oxide. Nitric oxide formation is stimulated by endotoxin, cytokines such as Tumor necrosis factor, and Interleukines. The stimulation is due to the activation of an inducible nitric oxide synthase, which transforms an amino acid L-arginine into nitric oxide in endothelial cells and macrophages. In the present study, administration of endotoxin (LPS, E. coli extract, 70 µg/kg, iv) in six unanesthesized ewes resulted in a decrease in the mean arterial blood pressure (MAP) by 38%, P<0.01 and an increase in cardiac index of P<0.05. Injection of 50 mg/kg of carboxy-PTIO, as an antidote, after an hour of endotoxin dose, reestablished the normal baseline values of the cardiovascular parameters considered in this study. This indicates that carboxy-PTIO is an efficient nitric oxide scavenger chemical of trapping nitric oxide immediately after its synthesis. Therefore, based on the current result, carboxy-PTIO can be used as one possible treatment agent against septic shock.


(Ethiopian Journal of Health Development: 2000, 14(1): 85-90)