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Beyond vasodilation: The antioxidant effect of adrenomedullin in Dahl salt-sensitive rat aorta

2005; Elsevier BV; Volume: 332; Issue: 3 Linguagem: Inglês

10.1016/j.bbrc.2005.05.034

1090-2104

Yuanning Cao, Kenji Kuwasako, Johji Kato, Toshihiko Yanagita, Toshihiro Tsuruda, Junichi KAWANO, Yasuko Nagoshi, Alex F. Chen, Akihiko Wada, Tatsuo Suganuma, Tanenao Eto, Kazuo Kitamura,

Nitric Oxide and Endothelin Effects

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 p22phox, suggesting that AM increased the NOS coupling and bioavailability of NO. AM possesses significant antioxidant properties that improve endothelial function.