Nitric oxide signaling and the regulation of myocardial function

Abstract

Nitric oxide, which is produced endogenously within cardiac myocytes by three distinct isoforms of nitric oxide synthase, is a key regulator of myocardial function. This review will focus on the regulation of myocardial function by each nitric oxide synthase isoform during health and disease, with a specific emphasis on the proposed end-targets and signaling pathways.

Epo and Non-hematopoietic Cells: What Do We Know?

“…Upon eNOS activation and NO binding to soluble guanylyl cyclase, PKG-induced phosphorylation of contractile protein machinery is induced (165). These effects of Epo were confirmed for isolated cells as well as in vivo in hearts after intravenous Epo administration.…”

Oxidative modulation of marcaine and lekoptin in H9C2 rat myoblasts

“…The role of NO generation by cardiomyocytes and the expression of NOS isoforms is still unclear. Cardiomyocytes have been reported to express two NOS isoforms , endothelial and inducible, in disease states [8][9][10] . It was also reported that cardiac cells express neither iNOS nor eNOS immunoreactivity in both infracted and normal myocardium [11][12][13].…”

Cardiac endothelium: More than just a barrier

“…(5) NO is a key regulator of excitationcontraction coupling in the cardiomyocytes and therefore of myocardial contractile function. (17) NO has also been shown to modulate heart rate, ß-adrenergic inotropic response, myocardial energetics and substrate metabolism. (12) NO effects are achieved via intracellular downstream mechanisms that have initially been thought to be mainly cyclic GMP (cGMP)-mediated, although it is now known that many of the effects of NO are cGMP-independent.…”

“…(12) NO effects are achieved via intracellular downstream mechanisms that have initially been thought to be mainly cyclic GMP (cGMP)-mediated, although it is now known that many of the effects of NO are cGMP-independent. (17) The contractile effects of NO depend on the intracellular location of its release and the end-targets of its signalling pathways, e.g. when NO signalling targets the L-type calcium channels in cardiomyocytes, a decreased calcium current ensues which leads to attenuated ß-adrenergic receptor stimulated contraction.…”

“…when NO signalling targets the L-type calcium channels in cardiomyocytes, a decreased calcium current ensues which leads to attenuated ß-adrenergic receptor stimulated contraction. (17) In addition to its effects on myocardial contractile function and metabolism, NO is regarded as a potent cardioprotective molecule, particularly in the context of ischaemiareperfusion injury and delayed ischaemic preconditioning. (10,11) In view of the major functional and protective effects that NO exerts in the heart, as well as its unique properties as an effi cient local messenger molecule (NO is a gas and free radical, and therefore highly diffusible and reactive), (18,19) it is imperative (10) that more studies focus on the cellular sources of cardiac NO with particular emphasis on those cell types between which paracrine communication is likely.…”