Elevated cardiac tissue level of aldosterone and mineralocorticoid receptor in diastolic heart failure: beneficial effects of mineralocorticoid receptor blocker
Elevated cardiac tissue level of aldosterone and mineralocorticoid receptor in diastolic heart failure: beneficial effects of mineralocorticoid receptor blocker
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DOI：
10.1152/ajpregu.00402.2006
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发表时间：
2007-02-01
影响因子：
2.8
通讯作者：
Hori, Masatsugu
中科院分区：
文献类型：
--
作者：
Ohtani, Tomohito;Ohta, Miho;Hori, Masatsugu
舒张性心力衰竭患者心脏组织醛固酮和盐皮质激素受体水平升高：盐皮质激素受体阻滞剂的有益作用。Am J Physiol Regul Integr Comp Physiol 292：R946-R954，2007.首次发表于2006年10月5日; doi：10.1152/ajpregu.00402.2006。心脏醛固酮水平尚未在舒张性心力衰竭（DHF）中进行评估，其在这种类型的心力衰竭中的作用仍不清楚。本研究旨在通过液相色谱-质谱法检测心脏醛固酮，并评估盐皮质激素受体阻滞剂对高血压DHF的影响。Dahl盐敏感大鼠从7周开始喂食8%NaCl饮食（高血压DHF模型），在13周时分为3组：降压剂量依普利酮治疗组（12.5或40 mg（中心点）kg（-1中心点）/天（-1））和未治疗组。Dahl盐敏感大鼠以0.3%NaCl饮食作为对照。心脏醛固酮检测DHF大鼠，而不是在对照组大鼠，与盐皮质激素受体的心室水平增加。对照组和DHF大鼠的心脏11-脱氧皮质酮、皮质酮和11-脱氢皮质酮水平没有差异，但与盐皮质激素受体具有亲和力的皮质酮的组织水平是醛固酮的1,000倍。DHF大鼠心室组织中未检测到醛固酮合成酶活性和CYP 11B 2 mRNA。依普利酮可减轻心室肥大、心室纤维化、心肌硬化和舒张异常，从而预防显性DHF。总之，DHF大鼠心肌醛固酮水平升高。然而，与皮质酮相比，其值非常低，并且没有证据表明增加心肌内源性醛固酮的产生。盐皮质激素受体的上调可能在DHF的发病机制中起中心作用，阻断盐皮质激素受体可能是DHF的有效治疗方案。
Elevated cardiac tissue level of aldosterone and mineralocorticoid receptor in diastolic heart failure: beneficial effects of mineralocorticoid receptor blocker. Am J Physiol Regul Integr Comp Physiol 292: R946-R954, 2007. First published October 5, 2006; doi: 10.1152/ajpregu.00402.2006.-Cardiac aldosterone levels have not been evaluated in diastolic heart failure (DHF), and its roles in this type of heart failure remain unclear. This study aimed to detect cardiac aldosterone by use of a liquid chromatographic-mass spectrometric method and to assess the effects of mineralocorticoid receptor blockade on hypertensive DHF. Dahl salt-sensitive rats fed 8% NaCl diet from 7 wk (hypertensive DHF model) were divided at 13 wk into three groups: those treated with subdepressor doses of eplerenone (12.5 or 40 mg(center dot)kg(-1 center dot)day(-1)) and an untreated group. Dahl saltsensitive rats fed 0.3% NaCl diet served as controls. Cardiac aldosterone was detected in the DHF rats but not in the control rats, with increased ventricular levels of mineralocorticoid receptor. Cardiac levels of 11-deoxycorticosterone, corticosterone, and 11-dehydrocorticosterone were not different between the control and DHF rats, but the tissue level of corticosterone that has an affinity to mineralocorticoid receptor was 1,000 times as high as that of aldosterone. Aldosterone synthase activity and CYP11B2 mRNA were undetectable in the ventricular tissue of the DHF rats. Administration of eplerenone attenuated ventricular hypertrophy, ventricular fibrosis, myocardial stiffening, and relaxation abnormality, leading to the prevention of overt DHF. In summary, the myocardial aldosterone level increased in the DHF rats. However, its value was extremely low compared with corticosterone, and no evidence for enhancement of intrinsic myocardial aldosterone production was found. The upregulation of mineralocorticoid receptor may play a central role in the pathogenesis of DHF, and blockade of mineralocorticoid receptor is likely an effective therapeutic regimen of DHF.