Angiotensin II type 2 receptor gene transfer elicits cardioprotective effects in an angiotensin II infusion rat model of hypertension
Angiotensin II type 2 receptor gene transfer elicits cardioprotective effects in an angiotensin II infusion rat model of hypertension
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DOI：
10.1152/physiolgenomics.00170.2004
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发表时间：
2004-11-17
影响因子：
4.6
通讯作者：
Raizada, MK
中科院分区：
文献类型：
--
作者：
Falcón, BL;Stewart, JM;Raizada, MK
血管紧张素II 2型受体（AT 2 R）在心血管生理学中的作用仍然难以捉摸。我们已经开发了一种体内慢病毒载体介导的基因转移系统来研究AT 2 R的生理功能。本研究的目的是在非遗传性高血压大鼠模型中确定AT 2 R是否影响心脏肥大以及心肌和血管周围纤维化。在5日龄Sprague-Dawley大鼠中心内注射含有AT 2 R或盐水的慢病毒载体。这导致心脏组织中AT 2 R的持续过度表达。在15周龄时，向动物输注200 ng。kg（-1）。min（-1）的血管紧张素II或生理盐水。这导致血压（BP）升高，在治疗2周时达到最大值，并与左心室壁厚度（LVWT）增加123%和心脏重量/体重比（HW/BW）增加129%相关。此外，心脏肥大的增加与心肌和血管周围纤维化分别增加300%和158%相关。AT 2 R的心脏转导导致LVWT衰减85%，HW/BW衰减91%，血管紧张素输注诱导的心肌纤维化减少43%。在没有高血压衰减的情况下观察到心脏病理学的这些改善。因此，我们的观察表明，在心脏中AT 2 R的长期表达减弱了非遗传性高血压大鼠模型中的心脏肥大和纤维化。
The role of the angiotensin II type 2 receptor (AT2R) in cardiovascular physiology remains elusive. We have developed an in vivo lentiviral vector-mediated gene transfer system to study the physiological functions of the AT2R. Our objectives in this study were to determine whether the AT2R influences cardiac hypertrophy and myocardial and perivascular fibrosis in a nongenetic rat model of hypertension. Lentiviral vector containing the AT2R or saline was injected intracardially in 5-day-old Sprague-Dawley rats. This resulted in a persistent overexpression of the AT2R in cardiac tissues. At 15 wk of age, animals were infused with either 200 ng . kg(-1) . min(-1) of angiotensin II or saline by implantation of a 4-wk osmotic minipump. This resulted in an increase in blood pressure ( BP) that reached maximal by 2 wk of treatment and was associated with a 123% increase in left ventricular wall thickness (LVWT) and a 129% increase in heart weight to body weight ratios (HW/BW). In addition, the increase in cardiac hypertrophy was associated with a 300% and 158% increase in myocardial and perivascular fibrosis, respectively. Cardiac transduction of the AT2R resulted in an 85% attenuation of LVWT, 91% attenuation of HW/BW, and a 43% decrease in myocardial fibrosis induced by angiotensin infusion. These improvements in cardiac pathology were observed in the absence of attenuation of high BP. Thus our observations indicate that long-term expression of the AT2R in the heart attenuates cardiac hypertrophy and fibrosis in a nongenetic rat model of hypertension.