Institut for Biomedicin

Christian Aalkjær

Pro-contractile action of the Na,K-ATPase/Src-kinase signaling pathway in the vascular wall.

Publikation: KonferencebidragPosterForskningpeer review

DOI

Aim: Na,K-ATPase is essential for maintaining the transmembrane ion gradient and might initiate various intracellular signaling. These signals possibly act through a modification of the local ion concentrations or via Src-kinase activation. It is known that inhibition of the α-2 isoform of Na,K-ATPase by ouabain elevates blood pressure. Consequently, ouabain was shown to potentiate arterial contraction in vitro. In contrast, we have demonstrated that siRNA-induced down-regulation of the α-2 isoform Na,K-ATPase expression reduced arterial sensitivity to agonist stimulation and prevented the effect of ouabain. Here we demonstrate results of our research on the mechanisms involved in the modulation of vascular wall contractility by ouabain-sensitive Na,K-ATPase.
Methods: The experiments were performed using rat mesenteric arteries in isometric myograph conditions. To inhibit kinase activity a Src-family selective tyrosine kinase inhibitor, PP2, and pNaKtide - a membrane-permeable small peptide which antagonizes ouabain-induced activation of Src-kinase were used.
Results: The pro-contractile action of ouabain is associated with activation of Src. This is supported by Western blot analyses showing activation of Src by ouabain and its inhibition by pNaKtide. Src was also activated by agonist (noradrenaline - NA) stimulation. Src-dependent potentiation of vasoconstriction was associated with sensitization of contractile machinery to [Ca2+]i, as evident from MYPT (myosin phosphatase targeting protein) phosphorylation assay. Down-regulation of the α-2 isoform Na,K-ATPase prevented the inhibitory effect of Src inhibitors on arterial contraction.
Conclusions: The pro-contractile action of ouabain-sensitive Na,K-ATPase inhibition is associated with Src-kinase inhibition suggesting the role of this signaling pathway in regulation of vascular tone and peripheral resistance.
OriginalsprogEngelsk
Udgivelsesår28 aug. 2015
Antal sider1
DOI
StatusUdgivet - 28 aug. 2015
BegivenhedFEPS 2015 - Kaunas, Litauen
Varighed: 26 aug. 201529 aug. 2015

Konference

KonferenceFEPS 2015
LandLitauen
ByKaunas
Periode26/08/201529/08/2015

Se relationer på Aarhus Universitet Citationsformater

ID: 94423949