Heparin has an inhibitory effect on endothelin-l synthesis and release by endothelial cells

Abstract

We studied the inhibitory effects of heparin on basal and agonist-induced endothelin-l biosynthesis and release from cultured bovine endothelial cells. Heparin dose-dependently and similarly inhibited endothelin-l release, inositol trisphosphate production, and intracellular free Ca2+ levels stimulated by thrombin. Hirudin fragment had an inhibitory effect on thrombin-induced endothelin-l release, whereas anti-thrombomodulin antibody had no effect. Heparin completely blocked phorbol ester-induced endo- thelin-l release, whereas it had a partial inhibitory effect on endothelin-l release stimulated by angiotensin and vasopressin. Northern blot analysis using complementary DNA for bovine preproendo- thelin-1 as a probe revealed that heparin reduced not only the basal but also the stimulated expression of preproendothelin-1 messenger RNA by thrombin and phorbol ester. These data suggest that heparin, in addition to its antithrombin effect, has an inhibitory effect on the biosynthesis and release of endothelin-l, possibly by inhibiting protein kinase C-dependent pathway. (Hypertension 1993;21:353-358) © 1993 American Heart Association, Inc.