内皮C型ナトリウレチンペプチドは,小循環器の流れと血圧を調節するためにペリサイトに作用する

Katarina Špiranec¹, Wen Chen¹, Franziska Werner¹

¹Institute of Physiology, University of Würzburg and Comprehensive Heart Failure Center, University Hospital Würzburg, Germany (K. Špiranec, W.C., S.C., F.W., T.N., F.K., P.E.-N., K. Schuh, M.K.).

Circulation

|April 8, 2018

まとめ

C型ナトリウレチンペプチド (CNP) は小血管の血流を調節する. 微血管細胞におけるCNPのガニリルサイクラゼ-B (GC-B) 受容体は,正常な血管抵抗と血圧の維持に不可欠である.

科学分野:

心血管の生理学
内分泌学
分子生物学

背景:

周辺血管抵抗は動脈血圧に大きく影響する.
内皮C型ナトリウレチンペプチド (CNP) は血管トーンに影響しますが,その正確な細胞標的は議論されています.
CNPによって活性化されるガニリルサイクラゼ-B (GC-B) 受容体は,血管の滑らかな筋肉細胞 (SMC) に存在します.

研究の目的:

微血管細胞におけるGC-B受容体の役割と,CNP媒介による血管拡張に対するその効果を調査する.
微小血管におけるCNP/GC-B/cGMPシグナリングが周辺抵抗と血圧を調節するかどうかを判断する.

主な方法:

内皮細胞 (Tie2-Cre) または微血管SMC/pericytes (PDGF-Rβ-CreERT2) で GC-B遺伝子の欠損を発生させたマウス.
腸内顕微鏡検査,侵襲的/非侵襲的血液動力学,ペリサイト信号分析を用いた.
腎臓の生理学を評価し,血圧の調節への影響を理解しました.

主要な成果:

CNPの血管拡張作用は小動脈と毛細血管で強まった.
GC- B受容体の発現は,内皮細胞と微血管壁細胞 (pericytes) で確認された.
マイクロ血管性SMCとペリサイトにおけるGC- Bの損失は,周辺抵抗と高血圧の上昇につながった.

結論:

内皮のCNPは,遠隔動脈と毛細血管の血流を調節するために不可欠です.
CNP-GC-B/cGMPの信号伝達は,正常なマイクロ血管抵抗と血圧を維持するために不可欠である.

キーワード:

動脈圧周期的なGMP ガニリルサイクラゼマイクロ循環ナトリウレティックペプチドペリサイト

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