ENDOTHELIN ANTAGONIST

ENDOTHELIN IS A POTENT VASOACTIVE PEPTIDE, RECENTLY DISCOVERED AS THE FORMERLY DESCRIBED ENDOTHELIAL CELL-DERIVED CONTRACTING FACTOR INVOLVED IN THE REGULATION OF VASCULAR TONE. ALTHOUGH ENDOTHELIN POSSESSES POTENT VASOCONSTRICTOR ACTIVITY IN VITRO, ITS ACTIONS IN VIVO APPEAR TO BE COMPLEX. IN THE SYSTEMIC AND RENAL VASCULAR BEDS, VASODILATION SEEMS TO BE THE INITIAL EFFECT. IN THE PULMONARY AND MESENTERIC VASCULAR BEDS, ENDOTHELIN PRODUCES VASOCONSTRICTION. ENDOTHELIN STIMULATES THE GROWTH OF SMOOTH MUSCLE CELLS AND MAY PLAY A ROLE IN ATHEROSCLEROSIS. AN ANTAGONIST OF ENDOTHELIN WILL SERVE TO CHARACTERIZE ITS RECEPTOR INTERACTION AND PHYSIOLOGICAL EFFECTS. ANALOGS WILL BE SYNTHESIZED AND TESTED FOR THE INHIBITION OF ENDOTHELIN ACTIONS ON VASCULAR CONDUCTANCE. A POSSIBLE THERAPEUTIC AGENT FOR ATHEROSCLEROSIS AND HYPERTENSION, AS WELL AS ACUTEINJURY AND SHOCK, MAY THUS BE DEVELOPED.