Effect of endothelin-1 on the adrenoreactivity of blood vessels and on the participation of G-proteins and protein kinase C in endothelin-1-induced vasoconstriction

Endothelin (ET) is a peptide produced by the cells of the vascular endothel ium and is one of the most effective endogenous vasoconstrictive agents. The first reports on its isolation, purification, and synthesis appeared in 1987-88 [2]. In the interim it has been shown that in the mammalian organism at least three types of endothelin (ET-1, ET2, and ET-3) are synthesized, of which only ET1 is of endothelial origin. The vascular smooth muscles respond to ET-1 by a slowly developing strong contraction. ET-1 interacting with a receptor has been shown to cause, like other vasoconstrictors, activation of the phosphatidylinosi tol cycle, mobilization of intracellular calcium (Ca2*), and activation of protein kinase C (PKC) [10,13]. However, there are also marked differences in the dynamics and pathways of the transfer of the intracellular signal [5,10]. Meanwhile, the study of the mechanism of action of ET-1 is not only of theoretical, but also of practical interest, since it has been suggested that ET directly participates in such pathological processes as the development of ischemic damage to the brain [6], changes in the neurosecretory processes, a reduction of afferent