Plasma membrane Ca2+-ATPase equals no NO

This editorial refers to ‘Endothelial nitric oxide synthase activity is inhibited by the plasma membrane calcium ATPase in human endothelial cells’ by M. Holton et al., pp. 440–448, this issue. Nitric oxide (NO) is now seen as an important player in both normal cellular and whole-body physiology and also in many diseases including numerous vascular diseases such as hypertension, artherosclerosis, diabetes, hypercholesterolaemia, and septic shock. NO is a cellular messenger produced by three isoforms of NO synthases (NOS): neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). Under physiological conditions, the main source of NO in vessels is eNOS located in the endothelial cells. eNOS is activated by the calcium/calmodulin complex and can be regulated by many protein partners and post-translational modifications such as multisite phosphorylation (mainly serine and threonine residues; Figure 1).1 NO has determinant roles because it stimulates vasodilation and inhibits both proliferation of smooth muscle cells and platelet aggregation.2,3 In that respect, vascular diseases are often associated with a decrease in NO levels leading to hypertension with vascular hyperreactivity and remodelling.4 Indeed, long-term blockade of NOS in rats with N(omega)-nitro-l-arginine methyl ester results in severe hypertension.5 In pulmonary arterial hypertension, NO is one of the main therapeutic targets.6,7