Adrenomedullin inhibits the endothelin production induced by urotensin II in rat vascular smooth muscle cells

The aim of this study was to observe the effects of adrenomedullin (ADM) on endothelin (ET) production induced by urotensin II (U II) in rat vascular smooth muscle cells (VSMCs). Cultured VSMCs which were incubated with U II (10⁻⁸ mol/L) and with various concentrations of ADM were used to measure the VSMCs ³H-TdR incorporation, the activity of extracellular signal-regulated kinase (ERK), the amount of ET mRNA and ET production in VSMCs. In this work we found that incubation with U II (10⁻⁸ mol/L) increased obviously the amount of ET mRNA in VSMCs and ET production in medium, however, co-incubation with ADM (10⁻¹⁰– 10⁻⁸ mol/L) and U II(10⁻⁸ mol/L) reduced the amount of ET mRNA by 15%, 24% and 45% (P< 0.01) respectively, compared with U II alone. The content of ET in medium was 14.13, 11.38 and 11.00 pg/mL. ADM alone (10⁻⁸ mol/L) had no effect on ET production in VSMCs. U II (10⁻⁸ mol/L) promoted the ³H-TdR incorporation and activity of ERK in VSMCs. ADM inhibited VSMCs ³H-TdR incorporation and activation of ERK in a concentration-dependent manner. Compared with U II group, after co-incubation with ADM (10⁻¹⁰–10⁻⁸ mol/L) and U II (10⁻⁸ mol/L) the VSMCs ³H-TdR incorporation was decreased by 7% (P > 0.05), 32% (P < 0.05) and 41% (P < 0.01), respectively, and the activity of ERK was decreased by 24% (P > 0.05), 32% (P < 0.05) and 36% (P < 0.05), respectively, in a concentration-dependent manner. The results show that in cultured VSMCs ADM inhibits ET mRNA expression, ET production and proliferation stimulated by U II, and that inhibitory effect of ADM on U II bioaction could be mediated through inhibiting MAPK pathway.