Increased organ blood flow in chronic endotoxemia is reversed by nitric oxide synthase inhibition

We evaluated regional blood flows in a hyperdynamic sepsis model and the reversal of increased flows by blockade of nitric oxide (NO) synthase. Seven awake sheep were continuously infused with Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng · kg^-1 · min^-1] for 48 h. The NO synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg) was injected after 24 h. Blood flows to systemic organs were determined with the radioactive microsphere technique. LPS induced elevation of cardiac index by 36% (P < 0.05) and a fall in systemic vascular resistance index by 37% (P < 0.05) at 0 h [time of L-NAME administration, 24 h after infusion of LPS had begun]. L-NAME administration normalized cardiac index [6.1 ± 0.5 at 4 h posttreatment, 6.1 ± 0.51 · min^-1 · m^-2 at -24 h (baseline)] and systemic vascular resistance index (1,333 ± 105 at 4 h posttreatment, 1,280 ± 163 dyn · s · cm^-5 · m² at -24 h) and reduced all regional blood flows to near-baseline levels for the remainder of the study period (24 h). O₂ consumption was unaffected by treatment.