Endothelium‐dependent contractions and endothelial dysfunction in human hypertension

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Abstract
The endothelium is a crucial regulator of vascular physiology, producing in healthy conditions several substances with a potent antiatherosclerotic properties. Accordingly, the presence of endothelial dysfunction is associated with subclinical atherosclerosis and with an increased future risk of cardiovascular events. A large body of evidence supports the fundamental role of nitric oxide (NO) as the main endothelium‐derived relaxing factor. However, in the presence of pathological conditions, such as hypertension, endothelial cells, in response to a number of agents and physical stimuli, become also a source of endothelium‐derived contracting factors (EDCFs), including endothelins and angiotensin II and particularly cyclooxygenase‐derived prostanoids and superoxide anions. These latter were at first identified as responsible for impaired endothelium‐dependent vasodilation in patients with essential hypertension. However, cyclooxygenase‐dependent EDCFs production is characteristic of the aging process, and essential hypertension seems to only anticipate the phenomenon. It is worth noting that both in aging and hypertension EDCF production is associated with a parallel decrease in NO availability, suggesting that this substance could be oxygen free radicals themselves. Accordingly, in hypertension both indomethacin, a cyclooxygenase inhibitor, and vitamin C, an antioxidant, increase the vasodilation to acetylcholine by restoring NO availability. In conclusion, hypertension is characterized by a decline in endothelial function, associated with a progressive decrease in NO bioavailability and increase in the production of EDCF. The mechanisms that regulate the balance between NO and EDCF, and the processes transforming the endothelium from a protective organ to a source of vasoconstrictor, proaggregatory and promitogenic mediators remain to be determined.British Journal of Pharmacology(2009)157,527–536; doi:10.1111/j.1476‐5381.2009.00240.xThis article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit:http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009