Sartório Carmem Luíza, Fraccarollo Daniela, Galuppo Paolo, Leutke Meike, Ertl Georg, Stefanon Ivanita, Bauersachs Johann
Medizinische Klinik und Poliklinik I, Universitätsklinikum Würzburg, Bayerische Julius-Maximilians-Universität Würzburg, Germany.
Hypertension. 2007 Nov;50(5):919-25. doi: 10.1161/HYPERTENSIONAHA.107.093450. Epub 2007 Sep 10.
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.
盐皮质激素受体阻断可改善心肌梗死（MI）后早期的死亡率。本研究调查了盐皮质激素受体阻断在大鼠心肌梗死后早期对血管的影响。在冠状动脉结扎后立即开始，雄性Wistar大鼠接受安慰剂或依普利酮（100 mg/kg/d）治疗。7天后，进行血流动力学评估并测定内皮功能。MI后心力衰竭大鼠主动脉环中乙酰胆碱诱导的最大舒张显著减弱，而依普利酮治疗可改善这种情况。各组间DEA-NO供体介导的非内皮依赖性舒张相似。MI大鼠主动脉中内皮型一氧化氮合酶磷酸化降低，依普利酮治疗可使其恢复。MI安慰剂大鼠主动脉中血管紧张素I诱导的血管收缩以及血管紧张素转换酶蛋白水平升高，而盐皮质激素受体抑制可使其降低。MI后主动脉活性氧生成以及NAD(P)H氧化酶亚基p22(phox)的表达增加，依普利酮治疗的大鼠中这些指标恢复正常。总之，盐皮质激素受体拮抗改善了MI后早期的内皮功能障碍。潜在机制包括抑制血管紧张素转换酶上调以及改善内皮型一氧化氮合酶衍生的一氧化氮生物利用度。
