[Is NO becoming a word from the heart?]

Nitric oxide (NO) is involved in,the endothelium-dependent relaxation of vascular smooth muscle. This messenger may also play a role in the regulation of cardiac contractility. Indeed, various targets for NO have been described in cardiac myocytes. Stimulation of the heterodimeric guanylyl cyclase by NO leads to the cGMP-dependent modulation of phosphodiesterases, cGMP-dependent protein kinase, and ionic channels. In addition, NO could regulate intracellular calcium homeostasis and mitochondrial respiration in a cyclic GMP-independent manner. In light of this variety of effects in the cardiac myocytes, it is not surprising that NO is often, but not always, found to modulate cardiac contractility. The endogenous production of NO, by constitutive isoforms of nitric oxide synthase (NOS) seems to participate in various aspects of cardiac homeostasis. For instance, myocardial NO-synthases can control the efficiency of the sympathetic and parasympathetic systems in the heart. The relevance of the different sources of NO in the heart is the object of ongoing research. Yet, NO may be viewed as a paracrine factor (when produced by the endothelium) and/or as an autocrine factor (when produced by the myocyte). The expression of an inducible isoform of NOS (iNOS) in various cardiac cell types, was shown to occur in both experimental and human cardiac pathologies, However, while the effects of iNOS induction have been described in detail in vitro, the pathophysiological consequences of iNOS induction in vivo are not fully understood. Thus, it is still unclear whether iNOS activity in the heart should be considered as beneficial or deleterious.