Selective iNOS Inhibition Is Superior to Norepinephrine in the Treatment of Rat Endotoxic Shock

摘要

S-methyl-isothiourea(SMT) is a potent inhibitor of NO synthase (NOS) with relative selectivity to- wards the inducible isoform(iNOS). We compared SMT and norepinephrine for the treatment of ex- perimental endotoxic shock. Anesthetized rats challenged intravenously with lipopolysaccharide (LPS), 10 mg/kg, were treated after 1 h with a 4-h infusion of norepinephrine (titrated to maintain blood pressure within baseline values), SMT at low dose (0.1 mg·kg~-1·h~-1), or at high dose(1 mg· kg~-1·h~-1), or an equivalent volume of saline(2 ml·kg~-1·h~-1). In saline-treated animals, LPS increased plasma nitrate and produced hypotension, low cardiac output(CO), lactic acidosis, and signs of liver and kidney dysfunction. Norepinephrine maintained blood pressure(BP) and reduced the fall in CO, without affecting lactic acidosis, organ dysfunction, and nitrate accumulation.