Clin Hypertens.  2016 ;22(1):20. 10.1186/s40885-016-0055-8.

Neuronal nitric oxide synthase in hypertension – an update

• Zhang YH

• KMID: 2380226
• DOI: http://doi.org/10.1186/s40885-016-0055-8

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 Ca2+ 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.

Keyword

Keywords; Hypertension; Nitric oxide; Neuronal nitric oxide synthase (nNOS); Cardiomyocyte; Hypertrophy

MeSH Terms

Angiotensin II
Biological Availability
Cardiomegaly
Cardiomyopathies
Consensus
Death, Sudden, Cardiac
Endothelium
Fibrosis
Guanylate Cyclase
Heart
Heart Failure
Homeostasis
Hypertension*
Hypertrophy
Muscle Cells
Myocardial Infarction
Myocardium
Myocytes, Cardiac
Myofibrils
NADPH Oxidase
Neurons*
Nitric Oxide
Nitric Oxide Synthase Type I*
Phosphorylation
Reactive Oxygen Species
Relaxation
Risk Factors
Stroke
Vasodilation
Angiotensin II
Guanylate Cyclase
NADPH Oxidase
Nitric Oxide
Nitric Oxide Synthase Type I
Reactive Oxygen Species