Endothelin‐1 modulates vascular smooth muscle structure and vasomotion: Implications in cardiovascular pathology

Endothelin‐1 modulates vascular smooth muscle tone by exerting potent vasoconstrictor actions through the ET A receptor subtype located on the membranes of vascular smooth muscle cells. This receptor subtype also mediates the growth‐promoting actions of this peptide in vascular smooth muscle cells. The ET A receptor is distinct, however, from the endothelin receptor subtype located on the endothelium; the anatomically and functionally distinct ET B receptor mediates the release of the endothelium‐derived factor nitric oxide, a labile substance which not only produces potent vasodilation but also possesses anti‐mitogenic activity. This report describes the interaction between these two vasoactive factors in the control of cardiovascular function. Under normal conditions the endothelium serves to modulate the contractile and proliferative actions of endothelin‐1. However, many cardiovascular disorders (e.g., hypertension, atherosclerosis, vascular restenosis, subarachnoid hemorrhage, etc.) are associated with both abnormal endothelial cell function, resulting in an inability to synthesize and/or release nitric oxide, and elevated circulating levels of endothelin‐1. Since the resultant loss/inhibition of nitric oxide will augment both the contractile and proliferative actions of endothelin‐1, this has the potential to promote vasoconstriction and smooth muscle hyperplasia/hypertrophy at the site of any such lesion. Since evidence is accumulating that both endothelin‐1 and nitric oxide play pivotal roles in the control of both vascular smooth muscle tone and growth, any imbalance between these two counter‐regulatory systems is likely to have profound pathological consequences within the cardiovascular system. © 1993 Wiley‐Liss, Inc.