Publikationsserver der Universitätsbibliothek Marburg

Titel:Funktionelle Bedeutung des TRPV4-Kationenkanals bei endothelvermittelten Vasodilatationsprozessen
Autor:Hartmannsgruber, Veronika
Weitere Beteiligte: Köhler, Ralf (Dr.)
Veröffentlicht:2010
URI:https://archiv.ub.uni-marburg.de/diss/z2010/0370
URN: urn:nbn:de:hebis:04-z2010-03705
DOI: https://doi.org/10.17192/z2010.0370
DDC:610 Medizin
Titel (trans.):Functional significance of cation channel TRPV4 in endothelial vasodilation
Publikationsdatum:2010-07-08
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Shear stress, Wandschubspannung, TRPV4, Vasodilatation, Trpv4 cation channel, EDHF, Vasodilation

Zusammenfassung:
Endotheliale Ionenkanäle und insbesondere Ca2+-permeable Kationenkanäle vom TRP-Typ sollen eine wichtige Rolle für die Endothelfunktion spielen, indem sie einen Calciumeinstrom erzeugen und somit wichtige Vasodilatationsysteme wie das NO-system und das EDHF-system stimulieren. Ziel der vorliegenden Arbeit war es, die funktionelle Bedeutung von osmo- und potentiell mechanosensitiven TRPV4-Kanälen für endotheliale Vasodilatationsprozesse zu charakterisieren. Hierzu sollten genetisch manipulierte Mäuse, denen das TRPV4-Protein fehlt, und korrespondiere Wildtyp-Tiere verwendet werden und vergleichende elektrophysiologische Untersuchungen an Endothelzellen und gefäßphysiologische Untersuchungen zur Endothelfunktion mittels des Druckmyographen durchgeführt werden. Die vergleichenden elektrophysiologischen Untersuchungen an Endothelzellen der A.c.c. von TRPV4+/+- und TRPV4-/--Tieren zeigten, dass TRPV4 AA- induzierte und HTS-induzierte Ströme wesentlich vermittelt. Die gefäßphysiologischen Befunde stellten heraus, dass durch Wandschubspannung und durch Reperfusion hervorgerufene Vasodilatation der Arteria carotis communis bei den TRPV4-/--Mäusen fehlten. Im Gegensatz dazu traten bezüglich der vom glatten Gefäßmuskel abhängigen SNP-vermittelten und der Azetylcholin-induzierten Vasodilatation zwischen TRPV4-/-- und WT- Mäusen keine Unterschiede auf. Diese Hauptbefunde der vorliegenden Arbeit legen nahe, dass endotheliale TRPV4-Kanäle eine essentielle Signaltransduktionskomponente bei der endothelialen Mechanotransduktion darstellen. Es kann ferner spekuliert werden, dass durch eine pharmakologische Modulation von endothelialen TRPV4-Kanälen der arterielle Gefäßtonus manipuliert werden kann. Dies könnte einen pharmakologischen Ansatzpunkt für eine neuartige antihypertensive Therapieform darstellen.

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