Homocysteine increases the synthesis of adrenomedullin in vascular fibroblasts of rats

The effect of homocysteine (Hcy) on the synthesis of adrenomedullin (ADM) was examined in vascular fibroblasts of rats to explore the possible activity of ADM in cardiovascular diseases. ADM from cultured vascular fibroblasts was measured by Radioimmunoassay (RIA) and was characterized by reverse phase high performance liquid chromatography. ADM mRNA in the fibroblasts was quantitated by competitive RT-PCR. The synthesis of ADM from vascular fibroblasts was increased by Hcy in a concentration dependent manner. ADM content in cultured medium increased by 68%-150% (P < 0.01,="" as="" compared="" to="" the="" control)="" when="" the="" fibroblasts="" were="" incubated="" in="" 50-200="" ol@l?1="" hcy="" for="" 12="" h,="" and="" the="" content="" increased="" by="" 55%-98%="" (p="">< 0.01)="" if="" the="" incubation="" lasted="" for="" 24="" h.="" hydrogen="" peroxide="" treatment="" also="" increased="" the="" synthesis="" of="" adm="" and="" it="" promoted="" adm="" synthesis="" synergetically="" with="" hcy.="" the="" changes="" of="" adm="" content="" were="" partially="" or="" completely="" inhibited="" by="" the="" antioxidant="" n-acetylcysteine="" (nac)="" treatment.="" hcy="" induced="" the="" increase="" of="" adm="" mrna="" and="" the="" amount="" of="" adm="" mrna="" was="" increased="" by="" 78%="" as="" compared="" with="" control="" (p="">< 0.05).="" nac="" almost="" completely="" inhibited="" the="" increase="" of="" adm="" mrna="" induced="" by="" hcy.="" in="" conclusion,="" hcy="" treatment="" up-regulated="" the="" expression="" of="" adm="" gene="" and="" increased="" the="" synthesis="" of="" adm="" in="" vascular="" fibroblasts.="" oxidative="" stress="" may="" be="" involved="" in="" the="" processes="" of="" the="" adm="" changes="" induce="" by="" hcy.="">