Adrenomedullin induces heme oxygenase-1 gene expression and cGMP formation in rat vascular smooth muscle cells.
Adrenomedullin (ADM) is a potent vasodilatory peptide. It regulates blood pressure by increasing cyclic adenosine monophosphate (cAMP) and guanosine-3',5'-monophosphate (cGMP). We sought to investigate the effect of ADM on heme oxygenase-1 (HO-1) gene expression and cGMP formation in cultured rat vascular smooth muscle cells (VSMCs). ADM treatment, 10(-9) and 10(-8) mol/L, increased cGMP production, and it increased the intracellular cGMP content of platelets coincubated with VSMCs. It increased cGMP content by 158.8% and 273.5%, respectively; increased HO-1 activity by 49.5% and 87%, respectively; augmented HO-1 protein levels by 66% and 126%, respectively; upregulated the steady-state level of HO-1 mRNA by 73% and 159%, respectively, and increased HO-1 mRNA transcription synthesis by four- and seven-fold, respectively. These results suggest that ADM induces HO-1 gene expression and cGMP formation in rat VSMCs.
Qi
Yong-Fen
YF
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, PR China. yongfenqi@yahoo.com
Dong
Lin-Wang
LW
Pan
Chun-Shui
CS
Zhang
Jing
J
Geng
Bin
B
Zhao
Jing
J
Tang
Chao-Shu
CS
D053607:Adrenomedullin; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology*
D010455:Peptides; D012333:RNA, Messenger; D014665:Vasodilator Agents; D053607:Adrenomedullin; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D006152:Cyclic GMP