The Effect of Combined Therapy with L-NAME and Vasoactive Amines on Acute Endotoxemia in Rats.

Abstract

Introduction: Sepsis and its potentially lethal complication, septic shock, are the most frequent causes of mortality, especially, in intensive care units. Cardiovascular changes are often don’t respond to conventional therapy, also the mechanisms by which sepsis leads to hemodynamic disturbance are not fully understood. A common cause of septic shock is gram negative bacterial infection. Nitric Oxide is a key mediator of hypotension, peripheral vasodilatation and vascular hyporeactivity to vasoconstrictor agents in endotoxemia. Objective: The aim of the present study is to verify the hemodynamic and biochemical responses to therapy with dopamine and dobutamine with or without a non-selective inhibitor of Nitric Oxide Synthase (NOS) in rats with shock-like syndrome. Hypothesis: We hypothesized that the inhibition of nitric oxide synthesis along with the intravenous infusion of vasoactives amines such as dopamine and dobutamine would reverse the hemodynamic status, optimizing heart performance without resulting in significant damage to platelet, renal and hepatical functions. Materials and Methods: An experimental model of endotoxic shock was induced in rats by means of intravenous infusion of bolus of lipopolyssaccharide derived from Escherichia coli ( 5 mg/kg ). We evaluated mean arterial blood pressure, heart rate, respiratory rate and urine output. Biochemical data such as platelet count, hepatic enzymes, urea and creatinine were also analysed. The treatment was carried out with the intravenous infusion of dopamine and dobutamine, both in doses of 10 μg/kg/min, through the use of an infusion pump with or without the intravenous bolus infusions of NG-nitro-L-arginine methyl ester ( 100 mg/kg ). Results: The results showed that the use of vasoactive amines dopamine and dobutamine, along with the infusion of bolus of NG-nitro-L-arginine methyl ester, improved the problem of hypotension caused by lipopolyssaccharide. It did not result in heart rate reduction, change in respiratory responses, or an increase in hepatic and renal disfunction. Conclusions: The inhibition of nitric oxide through by non-selective nitric oxide synthase pathways along with the infusion of dopamine and dobutamine can be a useful therapy in the treatment of septic shock.