Homocysteine increases the synthesis of adrenomedullin in vascular fibroblasts of rats

Homocysteine (Hcy), a highly reactive sulfur- containing amino acid, is an intermediate product of methionine metabolism. Elevation of plasma Hcy has been widely studied as an independent risk factor for many cardiovascular diseases such as atherosclerosis, thrombosis, etc.[1]. Inherited hyperhomocysteinemia cases usually suffer from occlusion or thrombosis in arteries and large veins before the age of 20. Hyperhomocysteinemia significantly reduces the survival rate[2] and dilatation functi…     

Adrenomedullin inhibits the endothelin production in-duced 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 (UⅡ) in rat vascular smooth muscle cells (VSMCs). Cultured VSMCs which were incubated with UⅡ (10-8 mol/L) and with various concentrations of ADM were used to measure the VSMCs 3H-TdR incorpora-tion, the activity of extracellular signal-regulated kinase(ERK), the amount of ET mRNA and ET production inVSMCs. In this work we found that incubation with UⅡ(10-8 mol/L) increased obviously the amount of ET mRNA inVSMCs and ET production in medium, however,co-incubation with ADM (10-10-10-8 mol/L) and UⅡ(10-8mol/L) reduced the amount of ET mRNA by 15%, 24% and45% (P< 0.01) respectively, compared with UⅡ alone. Thecontent 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 inVSMCs. UⅡ (10-8 mol/L) promoted the 3H-TdR incorpo-ration and activity of ERK in VSMCs. ADM inhibited VSMCs 3H-TdR incorporation and activation of ERK in aconcentration-dependent manner. Compared with UⅡgroup, after co-incubation with ADM (10-10-10-8 mol/L)and UⅡ (10-8 mol/L) the VSMCs 3H-TdR incorporation wasdecreased by 7% (P > 0.05), 32% (P < 0.05) and 41% (P <0.01), respectively, and the activity of ERK was decreasedby 24% (P > 0.05), 32% (P < 0.05) and 36% (P < 0.05), re-spectively, in a concentration-dependent manner. The resultsshow that in cultured VSMCs ADM inhibits ET mRNA ex-pression, ET production and proliferation stimulated by UⅡ, and that inhibitory effect of ADM on UⅡ bioaction could be mediated through inhibiting MAPK pathway.     

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 (UⅡ) in rat vascular smooth muscle cells (VSMCs). Cultured VSMCs which were incubated with UⅡ (10^-8 mol/L) and with various concentrations of ADM were used to measure the VSMCs ³H-TdR incorpora- tion, 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 UⅡ(10^-8 mol/L) increased obviously the amount of ET mRNA in VSMCs and ET production in medium, however, coincubation with ADM (10^-10—10^-8 mol/L) and UⅡ(10^-8 mol/L) reduced the amount of ET mRNA by 15%, 24% and 45% (P< 0.01) respectively, compared with UⅡ 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. UⅡ (10^-8 mol/L) promoted the 3H-TdR incorpo- ration and activity of ERK in VSMCs. ADM inhibited VSMCs 3H-TdR incorporation and activation of ERK in a concentration-dependent manner. Compared with UⅡ group, after coincubation with ADM (10^-10—10^-8 mol/L) and UⅡ (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), re- spectively, in a concentration-dependent manner. The results show that in cultured VSMCs ADM inhibits ET mRNA expression, ET production and proliferation stimulated by UⅡ, and that inhibitory effect of ADM on UⅡ bioaction could be mediated through inhibiting MAPK pathway.