Normal and dysfunctional endothelium
Since the landmark study of Furchgott and Zawadski in 1980, it has become well known that endothelium plays a critical part in modulating vascular tone in large conduit arteries as well as in the microcirculation.
Several studies have shown that the vasoactive effects of acetylcholine, serotonin, norepinephrine (noradrenaline), thrombin, substance P, adenine nucleotides, bradykinin, and endothelin result from a balance between their direct vasoconstrictor effects on the vascular smooth muscle and their indirect endotheliumdependent vasodilator effects.
When endothelium is intact and healthy, a net vasodilator effect predominates; however, when endothelium is structurally damaged or functionally abnormal, vasodilator responses to these endothelium-dependent vasodilators are attenuated, and paradoxical vasoconstriction can occur (Fig. below).