アンジオテンシンタイプ2受容体を介した血管弛緩機構

• 屋山 勝俊

  神戸学院大学薬学部生命薬学部門循環器薬理学研究室

• 岡本 博

  神戸学院大学薬学部生命薬学部門循環器薬理学研究室

書誌事項

タイトル別名

• Angiotensin Type 2 Receptor-Dependent Vasodilation
• アンジオテンシン タイプ 2 ジュヨウタイ オ カイシタ ケッカン シカン キコウ

抄録

  Angiotensin II (Ang II) signaling is mediated by two receptor subtypes, type 1 (AT₁) and type 2 (AT₂). The activation of AT₁ receptors is responsible for the development of Ang II-dependent hypertension, whereas the activation of AT₂ receptor is thought to play a counter-regulatory protective role in the regulation of blood pressure that opposes the AT₁ receptor-mediated vasoconstriction. However, the precise mechanisms by which increased numbers of AT₂ receptors counterbalance the AT₁-mediated actions of Ang II are unknown. We have demonstrated that the abdominal aortic banding in mice and rats and the 2-kidney, 1-clip Goldblatt model of hypertension in mice induces up-regulation of AT₂ receptors in the pressure-overloaded thoracic aorta. In these hypertensive animals, the AT₁-receptor antagonists but not calcium antagonist abolish up-regulation of the aortic AT₂ receptor as well as blood pressure elevation, suggesting that the pressure-overload up-regulates the aortic AT₂ receptor by Ang II via the activation of AT₁ receptor. Ang II binding to up-regulated AT₂ receptors induces vasodilation in these aortas through bradykinin B₂-receptor-mediated phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser⁶³³ and Ser¹¹⁷⁷ via a protein kinase A-dependent signaling pathway, resulting in sustained production of nitric oxide. These studies provide evidence that the vascular AT₂ receptor is up-regulated in the course of hypertension through the activation of AT₁ receptor, thereby activating a vasodilatory pathway in vessels through the AT₂ receptor via the bradykinin/nitric oxide/cGMP. This issue is important because the antihypertensive effect of AT₁-receptor blockers is, at least in part, dependent on AT₂-receptor activation.<br>

収録刊行物

• 薬学雑誌

  薬学雑誌 127 (9), 1357-1367, 2007-09-01

  公益社団法人 日本薬学会

キーワード

• hypertension
• angiotensin II
• AT₂ receptor
• bradykinin
• nitric oxide

詳細情報

• CRID: 1390282681106209792
• NII論文ID: 110006380721
• NII書誌ID: AN00284903
• DOI: 10.1248/yakushi.127.1357
• ISSN: 13475231
• ISSN: 00316903
• NDL書誌ID: 8937043
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I8937043
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/127/9/127_9_1357/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2008034097
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可