Nitric oxide stimulates adrenomedullin secretion and gene expression in endothelial cells.
Adrenomedullin, a peptide with vasorelaxant activity, stimulates nitric oxide (NO) synthesis. We tested whether or not NO regulates the function of the adrenomedullin system. Human umbilical vein endothelial cells (HUVEC) were incubated with the NO donors sodium nitroprusside (SNP), morpholinosydnonimine (SIN-1) and the phospodiesterase V inhibitor zaprinast. In HUVEC, adrenomedullin concentration in the supernatant was measured by radioimmunoassay and mRNA expression was studied by Northern blot and competitive quantitative PCR. SNP, SIN-1, and zaprinast (100 micromol/l each) significantly increased adrenomedullin concentration in the supernatant of HUVEC twofold. The same concentrations increased adrenomedullin mRNA expression four- to tenfold. Similar results were obtained by both quantitative PCR and Northern blot. Thus, NO donor exposure in vitro increases both adrenomedullin secretion and mRNA expression in a dose-dependent manner.
Dötsch
J
J
Klinik für Kinder und Jugendliche, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Deutschland. JoergWDoetsch@yahoo.com
Schoof
E
E
Hänze
J
J
Dittrich
K
K
Opherk
P
P
Dumke
K
K
Rascher
W
W
D053607:Adrenomedullin; D015152:Blotting, Northern; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010455:Peptides / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology
D020030:Nitric Oxide Donors; D010455:Peptides; D012333:RNA, Messenger; D053607:Adrenomedullin; D009569:Nitric Oxide