Vascular endothelium in ischemic heart disease: possible role for endothelium-derived relaxing factor.

The nature, mechanism of action, and roles of endothelium-derived relaxant factor (EDRF) are reviewed, particularly in relation to the coordination of vascular behavior in response to changes in flow, coronary spasm, and platelet aggregation. Vascular endothelium performs a multiplicity of roles. It is an active sieve for macromolecules and leukocytes, a negatively charged "lubricant" for passage of negatively charged red cells and platelets, and a factory for Von Willebrand factor, glycoaminoglycans, and plasminogen activator and its inhibitor. It is also a processing plant that metabolizes adenosine nucleotides to adenosine and activates angiotensin. Endothelium also produces prostacyclin and endothelium-derived relaxant factor, which act synergistically and through different pathways to the common ends of relaxing vascular smooth muscle and inhibiting platelet aggregation. Most recently it has been shown to also produce a constrictor agent called endothelin, a peptide whose structure has now been elucidated. This review will concentrate on EDRF, the recently discovered vasodilator agent that is continuously released by all vascular endothelium. It would be premature to define the role of EDRF in ischemic heart disease. It may, however, be timely to consider the ways in which EDRF might be relevant, based on a review of what is at present known.