Cyclic AMP regulates cytokine stimulation of endothelin-1 release in humanvascular smooth muscle cells

Exposure of human vascular smooth muscle cells (HVSMCs) to cytokines marked ly elevates endothelin-1 (ET-1) mRNA expression and peptide production. Cyc lic AMP is a key regulator of many physiological processes. The aim of this study was to determine whether an elevation of intracellular cAMP may affe ct cytokine-induced production of ET-1 in HVSMCs. Cicaprost, a prostacyclin analogue, forskolin, an activator of adenylnate cyclase, and Ro-20-1724, a phosphodiesterase type IV inhibitor, inhibited cytokine-stimulated ET-1 re lease in a concentration-dependent manner. Re-20-1724 also inhibited cytoki ne-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 pat hways may be involved in the regulation of cytokine-stimulated ET-I release from HVSMCs.