Mineralocorticoid receptor blockade improves vasomotor dysfunction and vascular oxidative stress early after myocardial infarction.
Mineralocorticoid receptor blockade improves mortality early after myocardial infarction (MI). This study investigated the vascular effects of mineralocorticoid receptor blockade in the early phase postinfarction in rats. Starting immediately after coronary ligation, male Wistar rats were treated with placebo or eplerenone (100 mg/kg/d). After 7 days, hemodynamic assessment was performed and endothelial function was determined. Maximum acetylcholine-induced relaxation was significantly attenuated in aortic rings from rats with heart failure after MI, and ameliorated by eplerenone treatment. Endothelium-independent relaxation by DEA-NONOate was similar among the groups. Endothelial NO synthase phosphorylation was reduced in the aorta of MI rats and restored by eplerenone therapy. Angiotensin I-induced vasoconstriction as well as angiotensin-converting enzyme protein levels were enhanced in aortas from MI placebo rats, and reduced by mineralocorticoid receptor inhibition. Aortic reactive oxygen species formation as well as the expression of the NAD(P)H oxidase subunit p22(phox) were increased after MI and normalized in eplerenone treated rats. In conclusion, mineralocorticoid receptor antagonism improved endothelial dysfunction in the early phase post-MI. Underlying mechanisms involve inhibition of vascular angiotensin-converting enzyme upregulation and improvement of endothelial NO synthase-derived NO bioavailability.
Sartório
Carmem Luíza
CL
Medizinische Klinik und Poliklinik I, Universitätsklinikum Würzburg, Bayerische Julius-Maximilians-Universität Würzburg, Germany.
Fraccarollo
Daniela
D
Galuppo
Paolo
P
Leutke
Meike
M
Ertl
Georg
G
Stefanon
Ivanita
I
Bauersachs
Johann
J
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000077545:Eplerenone; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology*; D019255:NADPH Oxidases / Q000378:metabolism; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects* / Q000503:physiopathology
D000451:Mineralocorticoid Receptor Antagonists; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D013148:Spironolactone; D000077545:Eplerenone; D019255:NADPH Oxidases; C515768:Cyba protein, rat