NOS 3 subcellular localization in the regulation of nitric oxide production

Abstract

Endothelium-derived nitric oxide (NO) is a key signalling molecule in the maintenance of cardiovascular health. Endothelial NO synthase (NOS 3), which catalyses the formation of NO, is targeted to the plasma membrane by dual acylation. In vitro studies suggest that membrane localization of NOS 3 is an important regulatory element of NO production. Dysfunction of the vascular endothelium and a decrease in NO bioavailability is associated with the development and progression of a number of cardiovascular diseases, including hypertension. Our laboratory has previously published that in salt-dependent hypertension there is an altered localization of NOS 3, with an increase in cytosolic expression. These data have led us to question whether the increased cytosolic NOS 3 expression is a form of compensation for endothelial dysfunction in hypertension, or an indicator and contributing factor to endothelial dysfunction. This review will outline the importance of subcellular localization in the regulation of NOS 3 in vitro, the role of NOS 3 in endothelial dysfunction associated with salt-dependent hypertension, and the potential physiological consequences of altered NOS 3 localization in vivo.