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 towards the inducible isoform (iNOS). We compared SMT and norepinephrine for treatment experimental endotoxic shock. Anesthetized rats challenged intravenously lipopolysaccharide (LPS), 10 mg/kg, were treated after 1 h 4-h infusion (titrated to maintain blood pressure within baseline values), at low dose (0.1 mg x kg-1 h-1), or high (1 an equivalent volume saline (2 ml h-1). In saline-treated animals, LPS increased plasma nitrate produced hypotension, cardiac output (CO), lactic acidosis, signs liver kidney dysfunction. Norepinephrine maintained (BP) reduced fall in CO, without affecting organ dysfunction, accumulation. The latter was dose-dependently blunted by SMT. Treatment this agent prevented through systemic vasoconstriction CO dose. Low, but not high, acidosis. Both doses renal, liver, additional studies, we obtained evidence that, contrast dose, did interfere function constitutive NOS. These findings suggest potential advantage selective iNOS inhibition over standard adrenergic support therapy septic