**2.2 Endothelin-1 (ET-1)**

ET-1 is a peptide of 21 amino acids that has two disulfide junctions, synthesized from a 39 amino acid precursor sequence named pre-pro endothelin by the activity of endothelin-converting enzyme (ECE) (**Figure 2**). ECE-1 restricts the synthesis of ET-1. The ET-1 its produced mainly in ECs, induced by several cytokines, angiotensin II and mechanical stress. It is codified by EDN1 gene, which expression is reduced by NO and prostaglandin I2 [7].

There are two basic types of ET-1 receptors: ETA and ETB. Both receptors are coupled to a G-protein and to the formation of IP3. ETA is, in normal conditions, the most prevalent of these ET-1 receptors [8].

ET-1 action is characterized by vasoconstriction; this effect is initiated once it binds to ETA receptor. The union of these results in the activation of Gq-PLC-IP3 pathway. IP3 induces the release of Ca2+ of the endoplasmic reticule by opening the L-type Ca2+ channels and increasing the cytosolic Ca2+, which produced the contraction of the muscular smooth cells and subsequent vasoconstriction (**Figure 3**) [1, 7, 8].

Despite the presence of ETB receptor on vascular smooth cells, it is also found on ECs, which stimulates the formation of NO causing vasodilatation, and additionally decreases the ET-1 synthesis causing relaxation [1].
