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

我们利用激光显微切割(LMD)技术建立了一种分离心肌和心脏血管的选择性和综合性基因表达谱分析方法。为探讨高血压前期药物干预对高血压形成的影响，对4~7周龄易卒中自发性高血压大鼠(SHR-SP)给予血管紧张素II受体阻滞剂(ARB)。早期接触ARB的SHR-SP在高血压阶段的血压显著低于未接受ARB治疗的SHR-SP。此外，早期暴露于ARB的SHR-SP的卒中发生率和全因死亡发生率显著低于未暴露ARB的SHR-SP。比较早期应用ARB和不应用ARB的SHR-SP心肌区和血管区的mRNA表达模式。采用自发性高血压大鼠去窦主动脉神经的方法建立高血压合并大鼠血压变异性(BPV)模型。在血压正常的大鼠中，BPV增加仅导致有限的心肌肥大和纤维化。相反，大的BPV加重了SHR的心肌肥大和纤维化，导致左心室收缩功能不全。研究发现，心肌内小动脉的慢性炎症引起了BPV诱导的心脏重塑的严重加重。分别在心肌区和血管区研究了高血压和大BPV联合诱导的基因表达谱变化。

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.