Nitric-Oxide And Endotoxemia

A number of recent publications have demonstrated that exposure of various cell types to bacterial lipopolysaccharide (LPS) results in the induction of an L-arginine-dependent nitric oxide (NO) producing pathway. In animal models, LPS-induced NO production and the subsequent increase in cGMP is a major factor associated with the hyporeactivity of both large conductance arteries and small resistance arteries to a wide range of vasoconstrictor agents. Although LPS can directly act on vascular smooth muscle cells to induce NO-synthase, endothelial cells (and probably other cells) accelerate the induction of vascular NO production and hyporeactivity to norepinephrine. Preliminary studies in patients with septic shock have demonstrated that inhibition of the L-arginine-NO-cGMP pathway can restore peripheral vascular resistance. When available, selective inhibitors of endotoxin-induced vascular NO production might be useful in the treatment of septic shock.