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

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 (SK_Ca), and the intermediate (IK_Ca) and the big (BK_Ca) conductance potassium channels in vascular function. In infra-renal aorta, endothelial SK_Ca and IK_Ca 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 BK_Ca 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 BK_Ca 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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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  -