Analysis of the Crosstalk between Myocardium and Vasculature:Mechanism of Prevention of Hypertension by Intervention in Prehypertensive Stage

我们建立了一个选择性和全面的基因表达模式分析分离心肌和血管在心脏中使用激光显微切割（LMD）的方法。为探讨高血压前期药物干预对高血压发展的影响，对4-7周龄的易卒中型自发性高血压大鼠（SHR-SP）给予血管紧张素II受体阻滞剂（ARB）。早期接受ARB治疗的SHR-SP在高血压阶段的血压明显低于未接受ARB治疗的SHR-SP。ARB早期暴露的SHR-SP的脑卒中发生率和全因死亡发生率均显著低于未暴露的SHR-SP。比较ARB早期暴露与未暴露SHR-SP心肌面积和血管面积mRNA表达的差异。通过对原发性高血压大鼠行去窦-主动脉神经术，建立了高血压和大血压变异性（BPV）复合的大鼠模型。在血压正常的大鼠中，BPV增加仅引起有限的心脏肥大和纤维化。相反，大BPV加重了SHR的心脏肥大和纤维化，导致LV收缩功能障碍。结果表明，心肌内小动脉的慢性炎症引起了大BPV引起的心脏重构加重。分别研究了高血压和大BPV组合特异性诱导的心肌区和血管区基因表达谱的变化。

We established a selective and comprehensive gene expression pattern analysis separating the myocardium and vasculature in the heart using the laser microdissection(LMD) method. To investigate the effects of pharmacological intervention at the prehypertensive phase on the development of hypertension, an angiotensin II receptor blocker(ARB) was administered to stroke-prone spontaneously hypertensive rats(SHR-SP) of 4-7 weeks old. SHR-SP with early exposure to ARB showed significantly lower blood pressure at hypertensive stage than those without ARB treatment. Also, the incidence of stroke and the incidence of all cause death were significantly lower in SHR-SP with ARB early exposure than those without ARB. The mRNA expression patterns of the myocardium area and vascular area were being compared separately between SHR-SP with and without ARB early exposure. A rat model of a combination of hypertension and large blood pressure variability(BPV) was created by performing a sino-aortic denervation in spoitaneously hypertensive rats. In normotensive rats, increased BPV induced only limited cardiac hypertrophy and fibrosis. In contrast, large BPV exaggerated cardiac hypertrophy and fibrosis, leading to LV systolic dysfunction in SHR. It was reveled that chronic inflammation of the intramyocardial arterioles elicited the large BPV-induced aggravation of cardiac remodeling. The gene expression profile changes induced specifically by a combination of hypertension and large BPV were being investigated separately in the myocardium area and vascular area.