Endothelium‐derived relaxing and contracting factors: New concepts and new findings

The vascular endothelium is a source of both relaxing and contracting factors. These yet to be identified substances have been termed endothelium‐derived relaxing factor(s) (EDRF) and endothelium‐derived contracting factor(s) (EDCF). The family of EDRF(s) appear to be important mediators of vascular relaxation and platelet disaggregation. Destruction of the endothelium or modulation of its structure, as occurs with coronary artery disease and atherosclerosis, results in impaired coronary and systemic arterial relaxation, vasospasm, and enhanced platelet aggregability. Acute and chronic hypertension blunts EDRF‐induced vascular relaxation. Thus, EDRF appears to represent an endogenous modulator system of vascular smooth muscle‐endothelium‐platelet interaction in humans. Recent evidence supports the possibility that one EDRF may be nitric oxide, whereas a second EDRF may stimulate sodium‐potassium ATP'ase. EDCF may be a family of at least three substances. One substance appears to be a low molecular weight polypeptide, is produced by hypoxia, and promotes a long‐acting vasoconstriction associated with increased calcium influx into vascular smooth muscle. The second EDRF is of unknown origin, is diffusable, released by anoxia and hypoxia, and may facilitate the action of the leukotrienes and lipoxygenase products on vascular smooth muscle. The remaining EDCF may be derived from the actions of lipoxygenases on arachidonic acid and appears to be released by vasoconstrictor agonists, stretch and potassium ion. Further research is required to elucidate the functional role and nature of EDCF(s) on vascular smooth muscle.