ENDOTHELIN CARDIOVASCULAR PHARMACOLOGY AN D PATHOPHYSIOLOGY

Multidisciplinary approaches including pharmacology, biochemistry, imm unology and rapidly developing molecular biology techniques have been instrumental in the gigantic leaps observed in the field of endothelin s in recent years. With the receptors cloned as well as proposed biosy nthetic pathways being rapidly elucidated, the role of endothelin in c ardiovascular homeostasis as well as in the ethiology of vascular path ologies may lead to the development of therapeutically useful agents. This review succinctly describes some of the important aspects of the biology of endothelins from the processing of pre-pro-endothelin-1 to the active moiety of endothelin-1. Furthermore, physiopathological con siderations are presented concerning the usefulness of mixed ET(A)/ET( B) receptors as opposed to selective ET(A) receptors. Moreover, distin ct endothelin-converting enzyme activity specific to particular organs is outlined. Finally, the nuclear and cytosolic calcium-mobilizing pr operties of ET-1 in the vascular smooth muscle are illustrated. As far as the contribution of endothelin in cardiovascular regulation is con cerned, a correlation attempt will be made between the results obtaine d in animal models and (SIC)