ENDOTHELIUM-DERIVED VASOACTIVE FACTORS IN HYPERTENSION - NITRIC-OXIDEAND ENDOTHELIN

Endothelium-derived nitric oxide: The endothelium is a source of vasoa ctive factors among which the most relevant are nitric oxide and endot helin. Nitric oxide is synthesized from L-arginine by a family of nitr ic oxide synthases and is a widespread biological mediator. It is impl icated in many physiological and pathophysiological processes, includi ng a variety of cardiovascular diseases like hypertension. Nitric oxid e and hypertension: The release of nitric oxide seems to be modulated by changes in blood pressure. However, the role of nitric oxide in hyp ertension is still controversial and seems to vary depending on the st age of the disease and the model studied. In spontaneous hypertension, the production of nitric oxide is increased but inefficacious, probab ly because of increased inactivation or scavenging. In the heart the p roduction of nitric oxide seems to be increased, probably as a compens atory mechanism against hypertension. In salt-induced hypertension, ni tric oxide production may be impaired. In human hypertension, pharmaco logical experiments reveal an impaired nitric oxide dilator mechanism. In pulmonary hypertension, the use of nitric oxide gas inhalation has been proposed as a future therapy for this condition. Endothelin: End othelin-1 is a potent vasoconstrictor peptide produced and released fr om endothelial cells. In isolated blood vessels, endothelin causes pro found contraction. The hemodynamic effects of endothelin can be explai ned by the activation of two endothelin receptors, ET(A) and ET(B). Th e relationship between endothelin and hypertension is not clear. Altho ugh plasma endothelin levels are normal in most patients with essentia l hypertension, the hypertensive blood vessel wall may contract more p rofoundly in response to the peptide; hence, endothelin antagonists ma y have antihypertensive effects in patients with hypertension.