Regulation of vascular tone and endothelial function and its alterations in cardiovascular disease

The endothelium, located between the circulating blood and the vascular smooth muscle cells, is exposed to physical, metabolic, hormonal and pharmaceutical influences, to which it reacts by secreting factors modulating the activity of the underlying vascular smooth muscle cells in a predominantly paracrine fashion.

Under physiological conditions, endothelial mediators promote, as an overall effect, vasodilatation, prevent the adhesion of platelets and monocytes and, in addition, inhibit the proliferation and migration of vascular smooth muscle cells. Complex interactions between the numerous endothelial mediators so far described allow the fine tuning of vascular reactivity and the adaptations of the vasculature to changing demands. Endothelial dysfunction, on the other hand, is characterized by enhanced vasoconstrictor responses and by increased risks of thrombus formation and atherosclerosis.

Ageing and chronic diseases such as hyperlipidemia, atherosclerosis and hypertension are typically associated with restrictions of endothelial function; in addition, some acute disorders seem to be mediated by the same pathomechanism. Certain drugs exert their vascular effects on the endothelial level by directly or indirectly supplying nitric oxide (nitrates and oestrogens) or by inhibiting the action of other endothelial mediators (calcium-channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers and endothelin antagonists). In conclusion, the endothelium holds a central regulatory role in vascular physiology and disease, and seems to be the target of relevant therapeutic interventions.