Nitric oxide synthase inhibitors.

In 1990, several studies reported that an enhanced formation of endogenous nitric oxide (NO) contributes to the hypotension caused by endotoxin and tumor-necrosis factor-α (TNFα) (1-3). In addition, it became apparent that this overproduction of NO also plays an important role in the pathophysiology of the vascular hyporesponsiveness to vasoconstrictor agents (also termed vasoplegia) (4,5). Since then, many studies have reported on the effects and side effects of NO synthase (NOS) inhibitors in animal models of shock. Prior to discussing the pharmacology of various classes of NOS inhibitors, this chapter will briefly introduce the physiological role(s) of NO as well as the various (beneficial as well as detrimental) roles of NO in animal models of septic shock.