Ohtani Tomohito, Ohta Miho, Yamamoto Kazuhiro, Mano Toshiaki, Sakata Yasushi, Nishio Mayu, Takeda Yasuharu, Yoshida Junichi, Miwa Takeshi, Okamoto Mitsuhiro, Masuyama Tohru, Nonaka Yasuki, Hori Masatsugu
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Japan.
Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R946-54. doi: 10.1152/ajpregu.00402.2006. Epub 2006 Oct 5.
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 x kg(-1) x day(-1)) and an untreated group. Dahl salt-sensitive 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.
舒张性心力衰竭（DHF）患者的心脏醛固酮水平尚未得到评估，其在这类心力衰竭中的作用仍不清楚。本研究旨在采用液相色谱-质谱法检测心脏醛固酮，并评估盐皮质激素受体阻断对高血压性DHF的影响。从7周龄开始喂食8%氯化钠饮食的 Dahl 盐敏感大鼠（高血压性DHF模型）在13周龄时被分为三组：接受亚降压剂量依普利酮治疗的组（12.5或40mg·kg⁻¹·d⁻¹）和未治疗组。喂食0.3%氯化钠饮食的 Dahl 盐敏感大鼠作为对照。在DHF大鼠中检测到心脏醛固酮，而对照大鼠中未检测到，同时盐皮质激素受体的心室水平升高。对照大鼠和DHF大鼠之间11-脱氧皮质酮、皮质酮和11-脱氢皮质酮的心脏水平没有差异，但与盐皮质激素受体具有亲和力的皮质酮组织水平是醛固酮的1000倍。在DHF大鼠的心室组织中未检测到醛固酮合成酶活性和CYP11B2 mRNA。给予依普利酮可减轻心室肥厚、心室纤维化、心肌僵硬和舒张异常，从而预防明显的DHF。总之，DHF大鼠的心肌醛固酮水平升高。然而，与皮质酮相比其值极低，且未发现心肌内源性醛固酮生成增加的证据。盐皮质激素受体的上调可能在DHF的发病机制中起核心作用，阻断盐皮质激素受体可能是DHF的一种有效治疗方案。
