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.
Highlights
According to World Health Organization, over 1 billion people are associated with hypertension worldwide and the number of subjects with such disorder rises significantly in aged group [1,2,3,4]
Hypertension is a common condition that leads to fatal cardiovascular complications such as myocardial infarction, stroke, sudden cardiac death and heart failure
Myocardial hypertrophy by sustained pressure-overload is the adverse remodeling in hypertension that predisposes to the apoptosis and fibrosis, malignant consequences upon pathogenic stimuli
Summary
According to World Health Organization, over 1 billion people are associated with hypertension worldwide and the number of subjects with such disorder rises significantly in aged group [1,2,3,4]. Accumulating evidence shows that nNOS up-regulation in diseased heart is cardiac protective: nNOS has been shown to inhibit xanthine oxidoreductase [43, 44] or NADPH oxidases [45, 46] and mitochondria production of ROS [47], as a result, reduces oxidative stress and suppresses adverse myocardial remodeling.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have