Kokubo Manabu, Uemura Arata, Matsubara Tatsuaki, Murohara Toyoaki
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hypertens Res. 2005 Jul;28(7):601-9. doi: 10.1291/hypres.28.601.
The spontaneously hypertensive rat (SHR) has been well established as a suitable model for studies of hypertension, but little is known about the processes of left ventricular (LV) hypertrophy and the changes in cardiac function in this model. The present study was designed to provide a noninvasive evaluation of the time-dependent alteration of cardiac function in male SHR at 4 to 24 weeks of age and age-matched Wistar-Kyoto rats (WKY). Echocardiographic studies were performed after blood pressure (BP) and heart rate (HR) were measured by a tail-cuff method. The body weight (BW) of SHR was lighter than that of WKY at all ages, and HR was consistently lower, with significantly elevated systolic BP from 4 weeks of age. In the echocardiographic study, LV mass at 4 weeks of age was similar between WKY and SHR, although the ratio of LV mass to BW was higher in SHR than WKY. The ejection fraction, fractional shortening (FS) and midwall FS did not differ between the two groups at 4 weeks, but after 8 weeks, these parameters were decreased in the SHR. The deceleration time was prolonged in SHR after 16 weeks and the E/A ratio was lowered at 12 weeks. We also analyzed the expression levels of calcineurin, which were found to be increased in both groups with age. These results suggest that calcineurin does not play a major role in the development of LV hypertrophy. Thus, in SHR, cardiac hypertrophy develops by 4 weeks of age, and systolic and diastolic dysfunction is evident at 2 to 3 months.
自发性高血压大鼠（SHR）已被公认为是研究高血压的合适模型，但对于该模型中左心室（LV）肥大的过程以及心脏功能的变化知之甚少。本研究旨在对4至24周龄雄性SHR以及年龄匹配的Wistar-Kyoto大鼠（WKY）心脏功能随时间的变化进行无创评估。在用尾套法测量血压（BP）和心率（HR）后进行超声心动图研究。SHR在所有年龄段的体重（BW）均低于WKY，且心率持续较低，从4周龄起收缩压显著升高。在超声心动图研究中，4周龄时WKY和SHR的左心室质量相似，尽管SHR的左心室质量与体重之比高于WKY。两组在4周时射血分数、缩短分数（FS）和室壁中层FS无差异，但8周后，SHR的这些参数降低。16周后SHR的减速时间延长，12周时E/A比值降低。我们还分析了钙调神经磷酸酶的表达水平，发现两组的钙调神经磷酸酶表达水平均随年龄增加。这些结果表明钙调神经磷酸酶在左心室肥大的发展中不发挥主要作用。因此，在SHR中，心脏肥大在4周龄时就已发生，2至3个月时收缩和舒张功能障碍明显。
