Regulation and functional consequences of endothelial nitric oxide formation

Since its discovery, endothelium-derived nitric oxide (NO) has become one of the most intensely investigated molecules in the field of cardiovascular physiology. Although initial investigations centred on the role of NO in mediating vasodilation and inhibition of platelet activation it has since become clear that this small, atypical signal molecule is also involved in regulating cell growth and proliferation as well as affecting the transcription of certain genes, the products of which have been implicated in the pathogenesis of such states as atherosclerosis and hypertension. Our understanding of the intracellular regulation of the NO synthases has also progressed and the constitutive endothelial enzyme is now known to be controlled by both intracellular Ca2+ and pH. In addition it would appear that this enzyme can also be upregulated in response to stimuli such as fluid shear stress and oestrogen. This review is intended to give the reader a glimpse of the multifaceted actions of endothelium-derived NO.