Abstract
The last two decades have witnessed great advances in our understanding of the role of the vascular endothelin (ET) system in the control of blood pressure. The role of ET as one of the most potent endothelium-derived vasoconstrictors is now complemented with a newly discovered role in vascular relaxation. The transcription of the ET genes in endothelial cells leads to the formation of preproET and big ET, which are further metabolized by ET converting enzymes into ET-1, -2, -3 and -4 isoforms. ET isoforms bind with different affinities to ETA and ETB2 receptors in vascular smooth muscle, and stimulate [Ca2+]i and other signaling mechanisms of smooth muscle contraction and growth. ET also binds to endothelial ETB1 receptors, which are coupled to increase production of vasodilator substances such as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor, and may also function in ET clearance. Despite the prominent effects of ET on vascular function and growth, the role of ET and its receptors in the regulation of blood pressure and in the pathogenesis of hypertension has not been clearly established. Some forms of moderate to severe hypertension in human and salt-dependent hypertension in experimental animals may show elevated levels of plasma or vascular ET; however, other forms of hypertension may show normal levels. Also, while ET antagonists could reverse some forms of experimental hypertension, their potential use in medicine needs to be carefully examined particularly with regard to their effectiveness and specificity.
Keywords: endothelium, smooth muscle, calcium, hypertension
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