Pharmacology of nitric oxide: molecular mechanisms and therapeutic strategies.

Abstract

NO is considered to be an ubiquitous endogenous system which takes part in body's homeostatic regulations and in pathological events. NO derives from a) the actions of enzymes, the NO Synthases (NOS), which are constitutives (endothelial NOS (eNOS) and nervous NOS (nNOS)) and generate small amounts of NO and have homeostatic functions: and b) from the actions of inducible NOS (iNOS), which generate large amounts of NO and exert protective actions against noxious agents but also toxic effects (e.g. inhibition of enzymes) through the production of peroxynitrite (ONOO-). Modulation of the L-Arg/NO system may be used to obtain favourable therapeutic results, either by promoting (e.g. with NO donors) or by reducing (e.g. with NOS inhibitors) the production of NO. The present chapter will consider two approaches and four groups of potential therapeutic agents: 1) The stimulation of NO production with; a) agents which improve the efficiency of the Kallikrein-Kinin System; b) NO donors. 2) The reduction of excessive NO production with: a) inhibitors of NO Synthases; b) agents that reduce the formation of reactive nitrogen/ oxygen species (RNS / ROS).