Search

The functions of the endothelium and the effects of hypertension, atherosclerosis, and diabetes on the endothelium are reviewed. The endothelium affects vascular tone by releasing vasodilators and modulating the effects of vasoactive substances such as catecholamines, bradykinin, serotonin, and angiotensin II. Relaxation of vascular smooth muscle depends upon a functionally intact endothelium and the release of the endothelium-derived relaxing factor nitric oxide. Endothelial cells also appear to release a hyperpolarizing factor that relaxes smooth muscle through activation of the sodium-potassium pump, and of the endothelium-dependent contracting factors. Similarities are found in the vascular injury resulting from hypertension, atherosclerosis, and diabetes. When these risk factors coexist, they can act synergistically and magnify the vascular injury. The endothelium appears to be one of the major targets for these forms of injury. Future therapeutic strategies will focus on ways to prevent, arrest, or reverse endothelial injury., The endothelium is the layer of cells forming the inner lining of the blood vessels. It plays a very important role in the control of cardiovascular function. A variety of substances released from the endothelium under different conditions affect the responses to vasodilators such as prostacyclin, and to vasoconstrictors such as catecholamines, bradykinin, serotonin, and angiotensin II. (Vasodilators cause blood vessels to relax and vasoconstrictors cause them to contract.) One endothelial product that appears to be important in the regulation of blood pressure, among other functions, is endothelium-derived relaxing factor (EDRF). Another substance released by the endothelium is an as-yet unidentified factor that causes blood vessel relaxation by activating the transport of electrically charged ions across the membrane of the smooth muscle of the vascular system. The actions of these substances are dependent on the presence of an intact endothelium, and when this portion of the vasculature is damaged, disturbances in blood pressure regulation are often exacerbated. Several disease conditions can cause injury to the endothelium, including hypertension (high blood pressure), diabetes, and atherosclerosis (the formation of fatty plaque deposits on the inner surface of blood vessels). The endothelial damage caused by these various conditions is very similar, and may reflect a common mechanism. When these risk factors co-exist, a synergistic effect is often observed, and the degree of vascular injury is greater than the sum of the individual components. Arrest, prevention, and reversal of endothelial damage will be a major therapeutic focus in the future. (Consumer Summary produced by Reliance Medical Information, Inc.)

Kidney failure is a long-term consequence of diabetes mellitus. It occurs in 40 percent of the patients with insulin-dependent-diabetes mellitus (IDDM) and less often in non-insulin-dependent diabetes mellitus (NIDDM). Diabetic nephropathy is evidenced by protein in the urine, high blood pressure and decreased glomerular filtration rate (GFR), the ability of the kidney to filter the blood. Diabetic nephropathy seems to occur in families, suggesting a genetic predisposition to kidney damage resulting from the physiological effect of the diabetes disease process itself. In addition, the altered chemical composition of kidney structures from the diabetic disease process causes changes in the kidney which contribute to the development of high blood pressure. Identification of individuals at risk because of a genetic predisposition to nephropathy may help prevent end stage kidney failure. Diabetic nephropathy begins with small but detectable changes. Subtle abnormal protein secretions in the urine and small increases in blood pressure may indicate the beginnings of kidney damage. Therefore, controlling high blood pressure can prevent the progression of damaging nephropathy. Since high blood pressure is directly associated with the development and progression of nephropathy, its treatment in the earliest stages is essential in diabetics, particularly insulin-dependent diabetics. Angiotensin-converting-enzyme inhibitors, a type of blood pressure lowering agent, offer the most protection from kidney injury caused by high blood pressure and diabetes.