Nitric oxide, nitric oxide synthase, and hypertensive vascular disease.

In normotension the endothelium produces mainly nitric oxide (NO) and prostacyclin, and the vasodilator and growth inhibitory influence predominates. Hypertension, however, is associated with a shift towards enhanced constriction and vascular hypertrophy. These effects are associated with an apparent decrease in the production of bioactive NO and concomitant increase in the generation of oxygen-derived free radicals, such as superoxide anions (O(2)-). While the enzymatic source of endothelial O(2)- has been debated intensely over the past few years, it may well turn out that the endothelial NO synthase is itself an important producer of O(2)-. Because the redox state of endothelial cells and, for example, the activation of redox-sensitive transcription factors is regulated by the balance between NO and O(2)- production, endothelial NO synthase may well be the most crucial enzyme determining the anti- or prohypertensive and eventually proatherogenic state of the vascular wall.