Silva Sebastião D, Zampieri Thais T, Ruggeri Adriana, Ceroni Alexandre, Aragão Danielle S, Fernandes Fernanda B, Casarini Dulce E, Michelini Lisete C
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo.
Circ J. 2015;79(6):1372-80. doi: 10.1253/circj.CJ-14-1179. Epub 2015 Mar 25.
Hyperactivity of the renin-angiotensin system (RAS) and functional deficits in hypertension are reduced after exercise training. We evaluate in arteries, kidney and plasma of hypertensive rats the sequential effects of training on vascular angiotensinogen, Ang II and Ang (1-7) content.
Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were trained or kept sedentary (S) for 3 months. After hemodynamic measurements (weeks 0, 1, 2, 4, 8 and 12), blood, arteries and kidneys were obtained to quantify the angiotensin content (HPLC) and angiotensinogen expression (Western Blotting). SHR-S vs. WKY-S exhibited elevated pressure, increased angiotensinogen and angiotensins' content in the renal artery with a high Ang II/Ang (1-7) ratio (~5-fold higher than in the femoral artery, kidney and plasma, and 14-fold higher than in the aorta). Training promptly reduced angiotensinogen expression and downregulated the RAS in the renal SHR artery (1st-12th week), with a specific reduction of the vasoconstrictor axis; significant reduction of the AngII/Ang (1-7) ratio (36%, T4-T8) occurred simultaneously with significant pressure fall (5%). In other SHR arteries, plasma and kidneys and in all WKY tissues, T-induced AngII and Ang (1-7) reductions were proportional, maintaining the AngII/Ang (1-7) ratio.
Vascular RAS is not equally expressed in vessels, having crucial importance in the renal artery. In the renal SHR artery, training downregulates the vasoconstrictor and preserves the vasodilator axis while in other tissues and plasma training reduces both RAS axes, thus maintaining the vasoconstriction/vasodilatation balance in a lower level.
运动训练后肾素 - 血管紧张素系统(RAS)的活性亢进以及高血压中的功能缺陷会有所减轻。我们在高血压大鼠的动脉、肾脏和血浆中评估训练对血管血管紧张素原、Ang II和Ang (1-7)含量的相继影响。
将自发性高血压大鼠(SHR)和Wistar - Kyoto大鼠(WKY)进行3个月的训练或保持久坐不动(S)状态。在进行血流动力学测量(第0、1、2、4、8和12周)后,采集血液、动脉和肾脏样本,以定量血管紧张素含量(高效液相色谱法)和血管紧张素原表达(蛋白质免疫印迹法)。SHR - S组与WKY - S组相比,血压升高,肾动脉中血管紧张素原和血管紧张素含量增加,Ang II/Ang (1-7)比值较高(比股动脉、肾脏和血浆中的比值高约5倍,比主动脉中的比值高14倍)。训练迅速降低了肾SHR动脉(第1至12周)中血管紧张素原的表达并下调了RAS,血管收缩轴有特异性降低;AngII/Ang (1-7)比值显著降低(36%,第4至8周),同时血压显著下降(5%)。在其他SHR动脉、血浆和肾脏以及所有WKY组织中,训练引起的AngII和Ang (1-7)降低是成比例的,维持了AngII/Ang (1-7)比值。
血管RAS在不同血管中的表达并不相同,在肾动脉中具有关键重要性。在肾SHR动脉中,训练下调血管收缩轴并保留血管舒张轴,而在其他组织和血浆中,训练降低了两个RAS轴,从而在较低水平维持血管收缩/血管舒张平衡。