Is NO becoming a word from the heart?

Nitric oxide (NO) is involved in,the endothelium-dependent relaxation of va scular smooth muscle. This messenger may also play a role in the regulation of cardiac contractility. Indeed, various targets for NO have been describ ed in cardiac myocytes. Stimulation of the heterodimeric guanylyl cyclase b y NO leads to the cGMP-dependent modulation of phosphodiesterases, cGMP-dep endent protein kinase, and ionic channels. In addition, NO could regulate i ntracellular 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 m odulate cardiac contractility. The endogenous production of NO, by constitu tive isoforms of nitric oxide synthase (NOS) seems to participate in variou s aspects of cardiac homeostasis. For instance, myocardial NO-synthases can control the efficiency of the sympathetic and parasympathetic systems in t he 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 (wh en produced by the endothelium) and/or as an autocrine factor (when produce d 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 hum an cardiac pathologies, However, while the effects of iNOS induction have b een described in detail in vitro, the pathophysiological consequences of iN OS induction in vivo are not fully understood. Thus, it is still unclear wh ether iNOS activity in the heart should be considered as beneficial or dele terious.