Regulation of endothelin-1 production by a thromboxane A2 mimetic in rat heart smooth muscle cells

摘要

Throiuhoxune A, (TXA,) and ET-1 have been known to piny important roles in modulating vascular contraction and growth. The present study was undertaken to examine the effect of TXA , on the induction of endothelin-l (ET-1) mRNA and protein levels in smooth muscle cells derived from rat heart. U-46610, a stable TXA2 mimetic, superinduced preproET-l mRNA in the presence of cyeloheximide in these cells. This effect could he blocked by SQ-2954K, a TXA j/prostaglandin IT, receptor antagonist and by actinomycin I), an RNA synthesis inhibitor. In addition, 117, a protein kinase (inhibitor, could abolish the induction. Transient transl'ection experiment revealed lluu the elevated liT-1 mRNA level after U-4o61l) treatment was a result of the activation of ET-1 gene activity. The elevated ET-1 message level was accompanied by increased BT-1 release into the cultured medium. These results show that the short-lived TXA2 can induce potent and long-lived HT-I. These findings support a potential role for ET-1 in the pathogenesis of coronary atherosclerosis and hypertension evoked by TXA.