Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 300, Issue 6, Pages H2035-H2043Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00552.2010
Keywords
nitric oxide; endothelium; aldosterone; reactive oxygen species
Funding
- Institut National de la Sante et de la Recherche Medicale (Inserm)
- Agence Nationale de la Recherche [ANR005-PCOD005]
- Fondation de France
- Centre de Recherche Industrielle et Technique
- European Section of the Aldosterone Council
- Societe Francaise d'Hypertension Arterielle/MSD
Ask authors/readers for more resources
Favre J, Gao J, Di Zhang A, Remy-Jouet I, Ouvrard-Pascaud A, Dautreaux B, Escoubet B, Thuillez C, Jaisser F, Richard V. Coronary endothelial dysfunction after cardiomyocyte-specific mineralocorticoid receptor overexpression. Am J Physiol Heart Circ Physiol 300: H2035-H2043, 2011. First published March 25, 2011; doi: 10.1152/ajpheart.00552.2010.-The deleterious effects of aldosterone excess demonstrated in cardiovascular diseases might be linked in part to coronary vascular dysfunction. However, whether such vascular dysfunction is a cause or a consequence of the changes occurring in the cardiomyocytes is unclear. Moreover, the possible link between mineralocorticoid receptor (MR)-mediated effects on the cardiomyocyte and the coronary arteries is unknown. Thus we used a mouse model with conditional, cardiomyocyte-specific overexpression of human MR (hMR) and observed the effects on endothelial function in isolated coronary segments. hMR overexpression decreased the nitric oxide (NO)-mediated relaxing responses to acetylcholine in coronary arteries (but not in peripheral arteries), and this was prevented by a 1-mo treatment either with an MR antagonist, vitamin E/vitamin C, or a NADPH oxidase inhibitor. hMR overexpression did not affect coronary endothelial NO synthase content nor its level of phosphorylation on serine 1177, but increased cardiac levels of reactive oxygen species, cardiac NADPH oxidase (NOX) activity, and expression of the NOX subunit gp91phox, which was limited to endothelial cells. Thus an increase in hMR activation, restricted to cardiomyocytes, is sufficient to induce a severe coronary endothelial dysfunction. We suggest a new paracrine mechanism by which cardiomyocytes trigger a NOX-dependent, reactive oxygen species-mediated coronary endothelial dysfunction.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available