ABSTRACT

References ...............................................................................................360

Nitric oxide (NO) is a free radical gas molecule produced by the activity of NO synthase (NOS). Three NOS isoforms have been described: Two constitutive isoforms are expressed in endothelial cells and central nervous system (eNOS and nNOS, respectively) [1, 2] among other tissues, and on the other hand, an inducible isoform is synthesized by several cell types (iNOS) [3, 4]. Although eNOS and nNOS are calcium dependent and produce low levels of NO in a very tightly controlled way [5], iNOS is calcium independent, and in response to proinflammatory stimuli, it generates NO very rapidly and at higher levels than the constitutive isoforms. NO plays different roles depending on the cell type in which it is produced. In general, it is a signaling molecule, playing neurotransmission properties in the central nervous system [6-9]. Immune cells generate NO during inflammation [10-17], and it is an immune effector against several microorganisms [14, 18-22]. In the vascular endothelium, it is synthesized by the constitutive calcium dependent NOS isoform (eNOS). It acts as a potent vasodilator and thus is key for the maintenance of vascular tone [23]. The main target of NO produced by the endothelial cells resides in the smooth muscle cell layer, namely the soluble guanylate cyclase, which produces cyclic GMP (cGMP) and induces vasorelaxation [24].