Artery Research

Volume 3, Issue 4, December 2009, Pages 191 - 191

P10.03 ENDOTHELIUM-SPECIFIC CALCIUM-ACTIVATED POTASSIUM CHANNELS: TARGETS FOR ALDOSTERONE

Authors
V. Griol-Charhbili1, A. Nguyen Dinh Cat1, G. Palais1, L. Loufrani2, D. Henrion2, N. Farman1, F. Jaisser1
1U872, Paris, France
2UMR CNRS 6188, Angers, France
Available Online 3 December 2009.
DOI
10.1016/j.artres.2009.10.134How to use a DOI?
Abstract

To define the vascular role of the mineralocorticoid receptor (MR) in cardiovascular pathophysiology, we generated a conditional transgenic mouse model with MR overexpression in the endothelium.

We previously described increase sensitivity to several vasoconstrictors in mesenteric arteries such as in aorta of mice over-expressing the MR in the endothelium (MR-EC) in presence of a normal relaxation to vasodilatators. In vivo, blood pressure (BP) was increased in awaked MR-EC mice, as compared to the controls (CT) (tail-cuff method).

We have investigated the role of the small (SKCa), and the intermediate (IKCa) and the big (BKCa) conductance potassium channels in vascular function. In infra-renal aorta, endothelial SKCa and IKCa channel blockade (Apamin 1 μM+TRAM-34 1 μM) unmasked an impaired relaxation to acetylcholine in MR-EC mice as compared to controls. Inhibition of the smooth muscle specific BKCa channel with Iberiotoxin (0.1 μM) blunted the higher phenylephrin-induced contractile response observed in MR-EC as compared to CT. These pharmacological data suggest that endothelial MR overexpression is associated with an increased activity of EDHF-mediating endothelial Ca-activated K channels and a functional decrease of the smooth-muscle BKCa channel activity. Western-blot analyses of the protein expression levels of these channel subunits were performed. None of them showed significant modulation, suggesting that channel activity, rather than expression level, is affected in this model.

MR activation specifically in endothelial cells is therefore associated with increased BP and altered vascular reactivity, in absence of renal collecting duct mediated MR effects. This may be related to ion channels remodeling.

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Journal
Artery Research
Volume-Issue
3 - 4
Pages
191 - 191
Publication Date
2009/12/03
ISSN (Online)
1876-4401
ISSN (Print)
1872-9312
DOI
10.1016/j.artres.2009.10.134How to use a DOI?
Open Access
This is an open access article distributed under the CC BY-NC license.

Cite this article

TY  - JOUR
AU  - V. Griol-Charhbili
AU  - A. Nguyen Dinh Cat
AU  - G. Palais
AU  - L. Loufrani
AU  - D. Henrion
AU  - N. Farman
AU  - F. Jaisser
PY  - 2009
DA  - 2009/12/03
TI  - P10.03 ENDOTHELIUM-SPECIFIC CALCIUM-ACTIVATED POTASSIUM CHANNELS: TARGETS FOR ALDOSTERONE
JO  - Artery Research
SP  - 191
EP  - 191
VL  - 3
IS  - 4
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2009.10.134
DO  - 10.1016/j.artres.2009.10.134
ID  - Griol-Charhbili2009
ER  -