Beyond vasodilation: the antioxidant effect of adrenomedullin in Dahl salt-sensitive rat aorta.
We have investigated the antioxidant effect of adrenomedullin (AM) on endothelial function in the Dahl salt-sensitive (DS) rat hypertension model. Dahl salt-resistant (DR) and DS rats were fed an 8% NaCl diet. In addition, the DS rats were subcutaneously infused with either saline or recombinant human AM for 4 weeks. Although systolic blood pressures measured weekly in AM- and saline-infused rats did not significantly differ, aortic O2*- levels were significantly (P<0.01) higher in the latter. Likewise, both endothelial nitric oxide synthase (eNOS) mRNA and protein were significantly higher in saline-infused DS rats. Infusion of AM reduced both O2*- and eNOS expression to levels comparable to those seen in DR rats. AM infusion also upregulated the gene expression of guanosine-5'-triphosphate cyclohydrolase I and downregulated the expression of p22(phox), suggesting that AM increased the NOS coupling and bioavailability of NO. AM possesses significant antioxidant properties that improve endothelial function.
Cao
Yuan-Ning
YN
First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Japan.
Kuwasako
Kenji
K
Kato
Johji
J
Yanagita
Toshihiko
T
Tsuruda
Toshihiro
T
Kawano
Junichi
J
Nagoshi
Yasuko
Y
Chen
Alex F
AF
Wada
Akihiko
A
Suganuma
Tatsuo
T
Eto
Tanenao
T
Kitamura
Kazuo
K
D053607:Adrenomedullin; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010455:Peptides / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D011994:Recombinant Proteins / Q000097:blood / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D000975:Antioxidants; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013481:Superoxides; D053607:Adrenomedullin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat