Nitric Oxide Synthase Function in Exercise

Pasquale      Pagliaro; Daniele      Mancardi; Claudia      Penna

Abstract

Endothelial cells (ECs) regulate blood flow and pressure, platelet aggregation, and angiogenesis. Chemical (e.g. acetylcholine, bradykinin) and mechanical stimuli (linear shear stress and pulse pressure) enhance endothelial production of nitric oxide (NO). In the mammalian three isoforms of NO synthase [endothelial (eNOS), inducible (iNOS) and neuronal (nNOS)] are expressed in different cell types showing a specific subcellular compartmentalization with colocalized effectors. The NOS-guanylyl-cyclase-protein kinase G (PKG) system plays a key role in mediating specific signaling involved in both short- and long-term control of several functions. In particular, mechanical-induced NO release may act as an amplifier of the local metabolic vasodilator(s) during exercise. It is likely that mechanical-induced increase in eNOS and extra-cellular superoxide dismutase expression and activity contribute to the augmentation of endothelial function during exercise training. NO-induced cGMP activates PKG, which phosphorylates other kinases to regulate their activity, leading to a reduction of cytosolic Ca2+ and, thus, to vascular relaxation. c-Src and other kinases are also activated and play a pivotal role as intracellular signaling molecules during exercise training, which may also lead to genomic and nongenomic changes. Endothelial dysfunction is a component of atherogenic activity, diabetes and other vascular risk factors which lead to coronary heart disease and heart failure. In patients, training may improve NO production that explains beneficial effects of exercise, such as lowered lipoprotein level, increased vasodilatation and reduced vasoconstriction. The improved outcomes may be due, in part, to the positive effect of exercise on NOSs function, kinase activation and, consequently, on endothelial dependent vasodilatation.

Keywords: Exercise, nitric oxide synthase, vasodilatation, endothelium, cGMP, PKC, c-Src, ERK