| First Author | Fujita M | Year | 2005 |
| Journal | Hypertension | Volume | 45 |
| Issue | 6 | Pages | 1165-72 |
| PubMed ID | 15867131 | Mgi Jnum | J:110042 |
| Mgi Id | MGI:3630362 | Doi | 10.1161/01.HYP.0000165690.85505.37 |
| Citation | Fujita M, et al. (2005) Sympatho-inhibitory action of endogenous adrenomedullin through inhibition of oxidative stress in the brain. Hypertension 45(6):1165-72 |
| abstractText | Central sympathetic activation is one of the possible mechanisms underlying hypertension, in which reactive oxygen species may play a role. Thus, we examined whether adrenomedullin, an antioxidant peptide, is involved in the central regulation of arterial pressure through sympatho-modulatory action. Adrenomedullin knockout mice were fed with high-salt diet for 4 weeks to stimulate adrenomedullin production. In the wild-type littermates, brain adrenomedullin content was significantly increased with salt loading, but not in the knockout mice. Intracerebroventricular hyperosmotic saline increased arterial pressure and sympathetic nerve activity in a dose-dependent fashion. With the normal salt diet, the hyperosmotic saline-induced response did not significantly differ between the knockout and wild-type mice; with the high-salt diet, however, the response was significantly greater in the knockout mice than in wild-type littermates (arterial pressure: 35.3+/-5.7% versus 20.1+/-2.1%, P<0.05; sympathetic nerve activity: 30.3+/-4.8% versus 15.9+/-1.5%, P<0.05; respectively). Moreover, pretreatment with 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol), a membrane-permeable superoxide dismutase mimetic, inhibited the augmented response to central hyperosmotic saline in salt-loaded knockout mice. Consistently, the hyperosmotic saline-induced production of reactive oxygen species, measured by the lucigenin chemiluminescence method, was significantly greater in the isolated hypothalamus of salt-loaded knockout mice than in that of salt-loaded wild-type ones. In conclusion, endogenous adrenomedullin in the brain may inhibit sympathetic activation through its antioxidant action. |
