Nitric oxide and septic shock.

1. Nitric oxide (NO) is generated by three different isoforms of NO synthase, two of which are expressed constitutively (in endothelium: eNOS, brain: nNOS), while one is induced by endotoxin (LPS) or cytokines (iNOS). 2. Expression of iNOS in many organs or tissues in septic shock (caused by Gram-negative or Gram-positive bacteria) results in an enhanced formation of NO that contribute to hypotension, vascular hyporeactivity to vasoconstrictors, organ injury, and dysfunction as well as host defense. 3. Inhibition of either the expression of iNOS protein (e.g., with dexamethasone) or of NOS activity (e.g., with selective inhibitors of iNOS activity) exerts beneficial effects in animal models of shock. In contrast, inhibition of eNOS activity may lead to excessive vasoconstriction (adverse effects). 4. There is limited evidence regarding the degree of iNOS induction in human cells or tissues with septic shock. Preliminary data from ongoing clinical trials indicate that nonselective inhibitors of NOS activity (e.g., NG-methyl-L-arginine [L-NMMA]) exert beneficial hemodynamic effects.