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Nitric oxide in the cardiovascular system: a simple molecule with complex actions.

Strijdom H, Chamane N, Lochner A - Cardiovasc J Afr (2009 Sep-Oct)

Bottom Line: However, due to various complex underlying cellular mechanisms, the actions of NO often seem to be contradictory.NO is a promising candidate molecule that could find therapeutic application.For this to be achieved, a sound understanding of this simple molecule and its complex actions is required.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, South Africa. jgstr@sun.ac.za

ABSTRACT
Since it was identified as the elusive endothelium-derived relaxing factor (EDRF) in the 1980s, nitric oxide (NO) has rapidly gained status as one of the most important signalling molecules in the cardiovascular system. Now, 20 years later, NO is regarded by most to be a ubiquitous mediator of cardioprotection. However, due to various complex underlying cellular mechanisms, the actions of NO often seem to be contradictory. This article sheds light on some of the mechanisms that may influence the variable actions of NO in the heart. Its role in conditions of oxygen deprivation (ischaemia and hypoxia) in particular is relevant to basic scientists and clinicians alike, since the prevalence of ischaemic heart disease is on the rise (in both the developed and the developing worlds) and novel therapeutic options are in constant demand. NO is a promising candidate molecule that could find therapeutic application. For this to be achieved, a sound understanding of this simple molecule and its complex actions is required.

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Related in: MedlinePlus

Subcellular localisation of NOS determines actions of NO . In the cardiomyocyte, eNOS associates with caveolae and L-type calcium channels, resulting in eNOS-derived NO inhibition of the channel and muscle relaxation. On the other hand, nNOS associates with the sarcoplasmic reticulum (SR ) and ryanodine receptors (RyR), leading to increased calcium release from the SR and muscle contraction.
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Figure 2: Subcellular localisation of NOS determines actions of NO . In the cardiomyocyte, eNOS associates with caveolae and L-type calcium channels, resulting in eNOS-derived NO inhibition of the channel and muscle relaxation. On the other hand, nNOS associates with the sarcoplasmic reticulum (SR ) and ryanodine receptors (RyR), leading to increased calcium release from the SR and muscle contraction.

Mentions: Beta-adrenergic stimulation of hearts of eNOS-/- knockout mice had positive inotropic effects, whereas in hearts of nNOS-/- knockout mice, negative inotropic effects were observed.17 The underlying mechanism of these apparent paradoxical effects of NO is thought to relate to the subcellular location of these two isoforms of NOS.8 Therefore, the spatial confinement of specific NOS isoforms to distinct locations in cardiac cells has important implications for the effects of NO on contractile function (Fig. 2).


Nitric oxide in the cardiovascular system: a simple molecule with complex actions.

Strijdom H, Chamane N, Lochner A - Cardiovasc J Afr (2009 Sep-Oct)

Subcellular localisation of NOS determines actions of NO . In the cardiomyocyte, eNOS associates with caveolae and L-type calcium channels, resulting in eNOS-derived NO inhibition of the channel and muscle relaxation. On the other hand, nNOS associates with the sarcoplasmic reticulum (SR ) and ryanodine receptors (RyR), leading to increased calcium release from the SR and muscle contraction.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3721819&req=5

Figure 2: Subcellular localisation of NOS determines actions of NO . In the cardiomyocyte, eNOS associates with caveolae and L-type calcium channels, resulting in eNOS-derived NO inhibition of the channel and muscle relaxation. On the other hand, nNOS associates with the sarcoplasmic reticulum (SR ) and ryanodine receptors (RyR), leading to increased calcium release from the SR and muscle contraction.
Mentions: Beta-adrenergic stimulation of hearts of eNOS-/- knockout mice had positive inotropic effects, whereas in hearts of nNOS-/- knockout mice, negative inotropic effects were observed.17 The underlying mechanism of these apparent paradoxical effects of NO is thought to relate to the subcellular location of these two isoforms of NOS.8 Therefore, the spatial confinement of specific NOS isoforms to distinct locations in cardiac cells has important implications for the effects of NO on contractile function (Fig. 2).

Bottom Line: However, due to various complex underlying cellular mechanisms, the actions of NO often seem to be contradictory.NO is a promising candidate molecule that could find therapeutic application.For this to be achieved, a sound understanding of this simple molecule and its complex actions is required.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, South Africa. jgstr@sun.ac.za

ABSTRACT
Since it was identified as the elusive endothelium-derived relaxing factor (EDRF) in the 1980s, nitric oxide (NO) has rapidly gained status as one of the most important signalling molecules in the cardiovascular system. Now, 20 years later, NO is regarded by most to be a ubiquitous mediator of cardioprotection. However, due to various complex underlying cellular mechanisms, the actions of NO often seem to be contradictory. This article sheds light on some of the mechanisms that may influence the variable actions of NO in the heart. Its role in conditions of oxygen deprivation (ischaemia and hypoxia) in particular is relevant to basic scientists and clinicians alike, since the prevalence of ischaemic heart disease is on the rise (in both the developed and the developing worlds) and novel therapeutic options are in constant demand. NO is a promising candidate molecule that could find therapeutic application. For this to be achieved, a sound understanding of this simple molecule and its complex actions is required.

Show MeSH
Related in: MedlinePlus