Cyclic AMP Regulates Cytokine Stimulation of Endothelin-1 Release in Human Vascular Smooth Muscle Cells

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Abstract
Summary: 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 cytokineinduced 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.

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