Woods M, Wood E G, Mitchell J A, Warner T D
Department of Cardiac, Vascular and Inflammation Research, St. Bartholomew's Hospital and the Royal London School of Medicine and Dentistry, London, UK.
J Cardiovasc Pharmacol. 2000 Nov;36(5 Suppl 1):S404-6. doi: 10.1097/00005344-200036051-00118.
Exposure of human vascular smooth muscle cells (HVSMCs) to cytokines markedly elevates endothelin-1 (ET-1) mRNA expression and peptide production. Cyclic AMP is a key regulator of many physiological processes. The aim of this study was to determine whether an elevation of intracellular cAMP may affect cytokine-induced production of ET-1 in HVSMCs. Cicaprost, a prostacyclin analogue, forskolin, an activator of adenylate cyclase, and Ro-20-1724, a phosphodiesterase type IV inhibitor, inhibited cytokine-stimulated ET-1 release in a concentration-dependent manner. Ro-20-1724 also inhibited cytokine-induced upregulation of preproendothelin-1 mRNA expression in saphenous vein (SV) vascular smooth muscle cells (VSMCs). These findings demonstrate that ET-1 mRNA expression and peptide production is modulated by elevations in cAMP levels. Further studies are necessary to elucidate which other pathways may be involved in the regulation of cytokine-stimulated ET-1 release from HVSMCs.
人血管平滑肌细胞（HVSMCs）暴露于细胞因子会显著提高内皮素-1（ET-1）的mRNA表达和肽生成。环磷酸腺苷（cAMP）是许多生理过程的关键调节因子。本研究的目的是确定细胞内cAMP升高是否会影响细胞因子诱导的HVSMCs中ET-1的生成。前列环素类似物西卡前列素、腺苷酸环化酶激活剂福斯可林以及磷酸二酯酶IV型抑制剂Ro-20-1724以浓度依赖的方式抑制细胞因子刺激的ET-1释放。Ro-20-1724还抑制细胞因子诱导的大隐静脉（SV）血管平滑肌细胞（VSMCs）中前内皮素-1 mRNA表达的上调。这些发现表明，ET-1的mRNA表达和肽生成受cAMP水平升高的调节。有必要进行进一步研究以阐明哪些其他途径可能参与调节细胞因子刺激的HVSMCs中ET-1的释放。
