2019年11月4日
Ser-Tyr and Asn-Ala, vasorelaxing dipeptides found by comprehensive screening, reduce blood pressure via different age-dependent mechanisms.
Aging
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- 巻
- 11
- 号
- 21
- 開始ページ
- 9492
- 終了ページ
- 9499
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.18632/aging.102400
To understand the changes in physiological responses due to aging, a number of bioactive probes based on different signal transduction pathways are necessary. In this study, we comprehensively and systematically investigated changes in blood vessel function with age using a 336-dipeptide library. In the early stage of hypertension, the most potent vasorelaxant dipeptide was Ser-Tyr (SY) in the mesenteric artery isolated from spontaneously hypertensive rats (SHR). SY-induced vasorelaxation and anti-hypertensive effects were blocked by L-NAME, an inhibitor of nitric oxide synthase (NOS), suggesting that SY activates the NO system. On the other hand, the patterns of dipeptides with vasorelaxation activity in early and advanced stages of hypertension were different. In the advanced stage, the most potent vasorelaxing dipeptide was Asn-Ala (NA). Orally administered NA (1.5 mg/kg) reduced the blood pressure in the advanced stage, at which drugs were sometimes less effective, and the anti-hypertensive effects lasted for 6 hr. The NA-induced vasorelaxation and anti-hypertensive activity was blocked by lorglumide, an antagonist of the cholecystokinin CCK1 receptor, suggesting that NA activated the CCK system. Taken together, in the early and advanced stages of hypertension, SY and NA exhibited vasorelaxing and anti-hypertensive effects via the NO and CCK systems, respectively.
- リンク情報
- ID情報
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- DOI : 10.18632/aging.102400
- PubMed ID : 31685714
- PubMed Central 記事ID : PMC6874431