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Hypertension. 1993;21:353-358

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Hypertension, Vol 21, 353-358, Copyright © 1993 by American Heart Association

ARTICLES

Heparin has an inhibitory effect on endothelin-1 synthesis and release by endothelial cells

T Imai, Y Hirata, T Emori and F Marumo
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.

We studied the inhibitory effects of heparin on basal and agonist- induced endothelin-1 biosynthesis and release from cultured bovine endothelial cells. Heparin dose-dependently and similarly inhibited endothelin-1 release, inositol trisphosphate production, and intracellular free Ca2+ levels stimulated by thrombin. Hirudin fragment had an inhibitory effect on thrombin-induced endothelin-1 release, whereas anti-thrombomodulin antibody had no effect. Heparin completely blocked phorbol ester-induced endothelin-1 release, whereas it had a partial inhibitory effect on endothelin-1 release stimulated by angiotensin and vasopressin. Northern blot analysis using complementary DNA for bovine preproendothelin-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-1, possibly by inhibiting protein kinase C-dependent pathway.


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