Background:The effects of hypertension and exercise training (T) on the sequential interplay between renin-angiotensin system (RAS), autonomic control and heart remodeling during the development of hypertension in spontaneously hypertensive rats (SHR), was evaluated.

Methods and Results:Time course changes of these parameters were recorded in 4-week-old SHR submitted to a T or sedentary (S) protocol. Wistar Kyoto rats served as controls. Hemodynamic recordings were obtained in conscious rats at experimental weeks 0, 1, 2, 4, and 8. The left ventricle (LV) was collected to evaluate RAS gene and protein expression, cardiomyocytes’ hypertrophy and collagen accumulation. Pre-hypertensive SHR exhibited augmented AT₁R gene expression; at 5 weeks, they presented with elevated pressure, increased LV angiotensinogen and ACE mRNA expression, followed by sympathoexcitation (from the 8^thweek onwards). Marked AT₁R protein content, myocytes’s hypertrophy, collagen deposition and increased pressure variability were observed in 12-week-old sedentary SHR. In addition to attenuating all these effects, T activated Mas receptor expression augmented parasympathetic modulation of the heart, and delayed the onset and reduced the magnitude, but did not block the development of genetic hypertension.

Conclusions:The close temporal relationship between changes in the LV ACE-Ang II-AT₁R axis, autonomic control and cardiac remodeling at both the establishment of hypertension and during exercise training reveals the essential role played by the AT₁R pathway in driving cardiac remodeling and autonomic modulation during the transition from the pre- to hypertensive phase.

背景：评估了高血压和运动训练（T）对自发性高血压大鼠（SHR）高血压发展过程中肾素-血管紧张素系统（RAS），自主控制和心脏重塑之间相继相互作用的影响。

方法和结果：这些参数的时程变化记录在提交给T或久坐（S）方案的4周龄SHR中。Wistar Kyoto大鼠作为对照。在实验第0、1、2、4和8周时在清醒大鼠中获得血流动力学记录。收集左心室（LV）评估RAS基因和蛋白表达，心肌细胞肥大和胶原蛋白积聚。高血压前期SHR表现出增强的AT ₁ R基因表达。在5周，它们呈现升高的压力下，增加的LV血管紧张素原和ACE mRNA的表达，随后sympathoexcitation（来自8^个星期起）。标为AT ₁在12周大的久坐性SHR中观察到R蛋白含量，心肌细胞肥大，胶原蛋白沉积和压力变异性增加。除了减弱所有这些作用外，T激活的Mas受体表达还增强了心脏的副交感神经调节，延迟了发作并降低了幅度，但并未阻止遗传性高血压的发展。

结论：高血压建立和运动训练期间，LV ACE-Ang II-AT ₁ R轴的变化，自主控制和心脏重塑之间的紧密时间关系揭示了AT ₁ R通路在驱动心脏方面的重要作用从高血压到高血压的过渡过程中的重塑和自主调节。