PATHOPHYSIOLOGY OF HYPERTENSION AND ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH DIABETES MELLITUS

Abstract

There is compelling evidence for endothelial dysfunction in both type 1 and type 2 diabetics. This dysfunction is manifest as blunting of the biologic effect of a potent endothelium-derived vasodilator, nitric oxide, and increased production of vasoconstrictors such as angiotensin II, ET-1, and cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. These agents and other cytokines and growth factors whose production they stimulate cause acute increases in vascular tone, resulting in increases in blood pressure, and vascular and cardiac remodeling that contributes to the microvascular, macrovascular, and renal complications in diabetes. Reactive oxygen species, overproduced in diabetics, serve as signaling molecules that mediate many of the cellular biochemical reactions that result in these deleterious effects. Adverse vascular consequences associated with endothelial dysfunction in diabetes mellitus are Decreased nitric oxide formation, release, and action Increased formation of reactive oxygen species Decreased prostacyclin formation and release Increased formation of vasoconstrictor prostanoid Increased formation and release of ET-1 Increased lipid oxidation Increased cytokine and growth factor production Increased adhesion molecule expression Hypertension Changes in heart and vessel wall structure Acceleration of the atherosclerotic process Treatment with antioxidants and with inhibitors of the renin-angiotensin system may reverse some of the pathologic vascular changes associated with endothelial dysfunction.