Abstract
Vascular upregulation of nitric oxide (NO) is an adaptive response to increased blood pressure that may help in the prevention of end-organ damage. Differences in cardiovascular and renal morbidity and mortality in hypertensive patients may result, at least in part, from individual variations in endothelial function in response to the hemodynamic workload of hypertension. A functional feedback balance exists between both angiotensin (Ang) II and NO under normal conditions. The NO-Ang II imbalance may not explain all the vascular pathophysiology of hypertension, but it certainly appears to be an important component. In hypertension, salt sensitivity, whether primary (ie, certain populations in the United States and Japan) or secondary (ie, aging, type II diabetes), appears to be a marker of increased cardiovascular and renal risk that is often linked to a decreased bioactivity of NO. In diabetes and atherosclerosis, NO-dependent vascular relaxation is impaired and can be restored by decreasing the synthesis and/or blocking the action of Ang II. An understanding of the relations between hypertension, cardiovascular risk factors, end-organ damage, and the NO-Ang II axis leads one to believe that the combination of therapeutic agents capable of reinstating the homeostatic balance of these vasoactive molecules within the vessel wall would be most effective in preventing or arresting end-organ disease.