Cardiac endothelin-1 plays a critical role in the functional deterioration of left ventricles during the transition from compensatory hypertrophy to congestive heart failure in salt-sensitive hypertensive rats
Cardiac endothelin-1 plays a critical role in the functional deterioration of left ventricles during the transition from compensatory hypertrophy to congestive heart failure in salt-sensitive hypertensive rats
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DOI：
10.1161/01.cir.98.19.2065
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发表时间：
1998-11-10
期刊：
影响因子：
37.8
通讯作者：
Sasayama, S
中科院分区：
文献类型：
--
作者：
Iwanaga, Y;Kihara, Y;Sasayama, S
背景 - 为了研究内源性内皮素 -1（ET -1）是参与左心室肥厚（LVH）的适应性过程，还是从左心室肥厚到充血性心力衰竭（CHF）的不良适应过程，我们使用了达尔盐敏感（DS）大鼠模型。在该模型中，全身性高血压在11周龄时导致代偿性向心性左心室肥厚，随后在17周龄时出现明显的左心室扩张和整体运动减弱。
方法与结果 - 通过特异性夹心酶免疫测定法，尽管左心室/体重比（LV/BW）显著增加，但与年龄匹配的达尔盐抵抗（DR）大鼠相比，左心室肥厚阶段的血清和心肌ET -1水平并未升高。然而，在充血性心力衰竭阶段，血清和左心室ET -1水平分别升高了3.8倍和5.4倍。左心室ET -1含量与体内经胸超声心动图测量的缩短分数（r = 0.763）和收缩期壁应力（r = 0.858）密切相关。免疫组织化学显示，左心室中显著增加的ET -1主要位于心肌细胞中。通过竞争性逆转录 - 聚合酶链反应，充血性心力衰竭大鼠的左心室前原内皮素 -1 mRNA水平升高了4.1倍。我们将11周龄的左心室肥厚大鼠随机分为三组，分别接受内皮素受体拮抗剂波生坦（Bos，100 mg·kg⁻¹·d⁻¹，n = 14）、α₁ - 受体拮抗剂多沙唑嗪（Dox，1 mg·kg⁻¹·d⁻¹，n = 12）或安慰剂（Cont，n = 14）慢性治疗。波生坦治疗在15周时未改变左心室的几何形状和功能；然而，它使左心室缩短分数的降低减少了51%（P <...（此处原文似乎不完整）
Background-To investigate whether endogenous ET-1 participates in an adaptive process of left ventricular hypertrophy (LVH) or a maladaptive process from LVH to congestive heart failure (CHF), we used a Dahl salt-sensitive (DS) rat model, in which systemic hypertension caused compensated concentric LVH at the age of 11 weeks followed by marked LV dilatation and global hypokinesis at the age of 17 weeks.Methods and Results-By specific sandwich enzyme immunoassay, serum and myocardial ET-1 levels at the LVH stage were not elevated compared with age-matched Dahl salt-resistant (DR) rats, despite the marked increase of LV/body weight ratio (LV/BW). However, at the CHF stage, serum and LV ET-1 levels increased by 3.8-fold and 5.4-fold, respectively. LV ET-1 contents had close relationships with the fractional shortening (r=0.763) and the systolic wall stress (r=0.858) measured by in vivo transthoracic echocardiography. Immunohistochemistry demonstrated that the remarkably increased ET-1 in LV is located mainly in cardiomyocytes. By competitive reverse transcriptase-polymerase chain reaction, LV prepro-ET-1 mRNA levels increased by 4.1-fold in CHF rats. We randomized 11-week-old LVH rats to chronic treatment with the endothelin receptor antagonist bosentan (Bos, 100 mg.kg(-1).d(-1), n=14), the alpha(1)-receptor antagonist doxazosin (Dox, 1 mg.kg(-1).d(-1), n=12), or vehicle (Cont, n=14). Bos treatment did not alter the LV geometry and function at 15 weeks; however, it attenuated the decrease of LV fractional shortening by 51% (P