期刊
CIRCULATION RESEARCH
卷 102, 期 5, 页码 607-614出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.107.162230
关键词
aging; clock gene; endothelial nitric oxide synthase
资金
- NIEHS NIH HHS [R01 ES005703] Funding Source: Medline
Impairment of circadian rhythmicity in the elderly has been suggested to cause age-associated diseases such as atherosclerosis and hypertension. Endothelium-derived nitric oxide (NO) is a critical regulator of cardiovascular homeostasis, but its production declines with aging, thereby inducing vascular dysfunction. We show here that impaired circadian rhythmicity is related to a decrease of NO production with aging. Treatment with an NO donor significantly upregulated the promoter activity of the clock gene Period via the cAMP response element-dependent and the E-box enhancer element-dependent pathways. Both phosphorylation and S-nitrosylation by NO are involved in this upregulation. In aged animals, endothelial NO synthase activity was markedly decreased during the daytime, along with impairment of clock gene expression and the circadian variation in blood pressure. Treatment of aged animals with an NO donor significantly improved the impairments. Inhibition of NO synthase activity also led to impairment of clock gene expression and blood pressure rhythm. These results suggest that NO is a key regulator of the circadian clock in the cardiovascular system and may be a novel target for the treatment of age-associated alteration of circadian rhythms.
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