Endothelial Mechanisms Regulating Blood Flow

Since the 1970s, the vascular endothelium has been known to have an important role in the regulation of smooth muscle function and in modulating leukocyte and platelet adhesion to the endothelium. As shown in the figure, various blood borne substances that come in contact with vascular endothelial cells (EC) cause the production and release of endothelial factors that elicit contraction (+) or relaxation (-) of vascular smooth muscle (VSM). These endothelial factors modulate the effects of norepinephrine (NE) released by sympathetic nerves (SN), and the effects of tissue metabolites and humoral factors.

The three most important endothelial-derived substances are: nitric oxide (NO), endothelin (ET-1), and prostacyclin (PGI₂).  NO and PGI₂ act as vasodilators, whereas ET-1 serves as a vasoconstrictor.

Damage to the vascular endothelium due to atherosclerotic processes or following ischemia and reperfusion alters the formation and release of endothelial factors.  When endothelial damage occurs, the endothelium produces less nitric oxide and prostacyclin, which causes the adrenergic vasoconstrictor tone to be unopposed.  This can lead to increased vascular tone and vasospasm.   Furthermore, decreased production of both of these endothelial factors can lead to increased platelet adhesion and aggregation, and therefore enhanced thrombogenesis.

RK Revised 04/06/2007