盐皮质激素受体拮抗剂改善心肌梗死后内皮功能障碍

fadi99

Mineralocorticoid Receptor Blockade Improves Vasomotor Dysfunction and Vascular Oxidative Stress Early After Myocardial Infarction

Carmem Luíza Sartório; Daniela Fraccarollo; Paolo Galuppo; Meike Leutke; Georg Ertl; Ivanita Stefanon; Johann Bauersachs

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 p22phox 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.
Hypertension. 2007;50:919-925
盐皮质激素受体拮抗剂改善心肌梗死 (MI)后早期死亡率。该研究分析了盐皮质激素受体拮抗剂对心肌梗死大鼠的早期血管效应。