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Clinical Hypertension

, 22:20

First Online: 03 November 2016Received: 15 July 2016Accepted: 19 October 2016

Abstract

Hypertension is a prevalent condition worldwide and is the key risk factor for fatal cardiovascular complications, such as stroke, sudden cardiac death and heart failure. Reduced bioavailability of nitric oxide NO in the endothelium is an important precursor for impaired vasodilation and hypertension. In the heart, NO deficiency deteriorates the adverse consequences of pressure-overload and causes cardiac hypertrophy, fibrosis and myocardial infarction which lead to fatal heart failure and sudden cardiac death. Recent consensus is that both endothelial and neuronal nitric oxide synthases eNOS or NOS3 and nNOS or NOS1 are the constitutive sources of NO in the myocardium. Between the two, nNOS is the predominant isoform of NOS that controls intracellular Ca homeostasis, myocyte contraction, relaxation and signaling pathways including nitroso-redox balance. Notably, our recent research indicates that cardiac eNOS protein is reduced but nNOS protein expression and activity are increased in hypertension. Furthermore, nNOS is induced by the interplay between angiotensin II Ang II type 1 receptor AT1R and Ang II type 2 receptor AT2R, mediated by NADPH oxidase and reactive oxygen species ROS-dependent eNOS activity in cardiac myocytes. nNOS, in turn, protects the heart from pathogenesis via positive lusitropy in hypertension. Soluble guanylate cyclase sGC-cGMP-PKG-dependent phosphorylation of myofilament proteins are novel targets of nNOS in hypertensive myocardium. In this short review, we will endeavor to overview new findings of the up-stream and downstream regulation of cardiac nNOS in hypertension, shed light on the underlying mechanisms which may be of therapeutic value in hypertensive cardiomyopathy.

KeywordsHypertension Nitric oxide Neuronal nitric oxide synthase nNOS Cardiomyocyte Hypertrophy AbbreviationsAng IIAngiotensin II

AT1RAng II type 1 receptor

BH4Tetrahydrobiopterin

CaMCalmodulin

cGMPCyclic guanosine monophosphate

cMyBPCMyosin binding protein C

cNOSConstitutive nitric oxide synthases

cTnITroponin I

eNOSEndothelial nitric oxide synthases

FADFlavin adenine dinucleotide

FMNFlavin mononucleotide

LVLeft ventricular

nNOS or NOS1Neuronal nitric oxide synthases

NONitric oxide

PKGProtein kinase G

PP2AProtein phosphatase 2A

RVRight ventricular

RyRRyanodine receptors

SERCACa ATPase in the SR

sGCSoluble guanylate cyclase

SNOS-nitrosothiol

SRSarcoplasmic reticulum

TACTransverse aortic constriction

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Author: Yin Hua Zhang

Source: https://link.springer.com/article/10.1186/s40885-016-0055-8







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