Imbalance of Endothelium-derived Relaxing and Contracting Factors: A New Concept in Hypertension?

The endothelium has a strategical anatomical position between the circulating blood and vascular smooth muscle cells. It has recently been recognized that endothelial cells play an important regulatory role in the circulation. The cells metabolize or activate vasoactive hormones (ie, norepinephrine, serotonin, bradykinin, angiotensin II), produce substances involved in coagulation and can release endothelium-derived relaxing factors and contracting factors. Nitric oxide and prostacyclin are vasodilators and inhibitors of platelet function. Endothelin is the most potent vasoconstrictor substance known. Thus, the endothelium can profoundly affect platelet adhesion and aggregation, vascular smooth muscle tone and possibly also vascular smooth muscle growth. Under physiological conditions, endothelium-derived relaxing factors appear to dominate. In contrast, in hypertensive and atherosclerotic arteries the release of endothelium-derived relaxing factors and/or the responsiveness of vascular smooth muscle cells to the relaxing factors is reduced, while that of endothelium-derived contracting factors is augmented. This imbalance of endothelium-derived relaxing and contracting factors may be important in the pathogenesis of hypertension and its cardiovascular complications.