Endothelial dysfunction: a strategic target in the treatment of hypertension?
Endothelial dysfunction is a common feature of hypertension, and it results from the imbalanced release of endothelium-derived relaxing factors (EDRFs; in particular, nitric oxide) and endothelium-derived contracting factors (EDCFs; angiotensin II, endothelins, uridine adenosine tetraphosphate, and cyclooxygenase-derived EDCFs). Thus, drugs that increase EDRFs (using direct nitric oxide releasing compounds, tetrahydrobiopterin, or L-arginine supplementation) or decrease EDCF release or actions (using cyclooxygenase inhibitor or thromboxane A2/prostanoid receptor antagonists) would prevent the dysfunction. Many conventional antihypertensive drugs, including angiotensin-converting enzyme inhibitors, calcium channel blockers, and third-generation beta-blockers, possess the ability to reverse endothelial dysfunction. Their use is attractive, as they can address arterial blood pressure and vascular tone simultaneously. The severity of endothelial dysfunction correlates with the development of coronary artery disease and predicts future cardiovascular events. Thus, endothelial dysfunction needs to be considered as a strategic target in the treatment of hypertension.
Tang
Eva H C
EH
Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Ave Louis Pasteur, NRB741, Boston, MA 02115, USA. htang@rics.bwh.harvard.edu
Vanhoutte
Paul M
PM
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002118:Calcium / Q000008:administration & dosage / Q000009:adverse effects; D015226:Dinucleoside Phosphates / Q000494:pharmacology; D019332:Endothelin-1 / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D045462:Endothelium-Dependent Relaxing Factors; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000502:physiology; D044023:Receptor, Endothelin B / Q000502:physiology; D017482:Receptors, Thromboxane / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
D000959:Antihypertensive Agents; D015226:Dinucleoside Phosphates; D019332:Endothelin-1; D045462:Endothelium-Dependent Relaxing Factors; D017382:Reactive Oxygen Species; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; C529314:uridine adenosine tetraphosphate; D000804:Angiotensin II; D011451:Prostaglandin-Endoperoxide Synthases; D002118:Calcium