Wolf Annemarie, Kutsche Hanna Sarah, Atmanspacher Felix, Karadedeli Meryem Sevval, Schreckenberg Rolf, Schlüter Klaus-Dieter
Department of Medicine, Institute of Physiology, Justus Liebig University Giessen, Giessen, Germany.
Front Physiol. 2021 Mar 23;12:598723. doi: 10.3389/fphys.2021.598723. eCollection 2021.
Obesity and hypertension are common risk factors for cardiovascular disease whereas an active lifestyle is considered as protective. However, the interaction between high physical activity and hypertension is less clear. Therefore, this study investigates the impact of high physical activity on the muscular and hepatic expression of glucose transporters (Glut), uncoupling proteins (UCPs), and proprotein convertase subtilisin/kexin type 9 (PCSK9) in spontaneously hypertensive rats (SHRs). Twenty-four female rats (12 normotensive rats and 12 SHRs) were divided into a sedentary control and an exercising group that had free access to running wheels at night for 10 months. Blood samples were taken and blood pressure was determined. The amount of visceral fat was semi-quantitatively analyzed and Musculus gastrocnemius, Musculus soleus, and the liver were excised. Acute effects of free running wheel activity were analyzed in 15 female SHRs that were sacrificed after 2 days of free running wheel activity. M. gastrocnemius and M. soleus differed in their mRNA expression of , , , and . Hypertension was associated with lower levels of and mRNA in the M. gastrocnemius, but increased expression of and in the M. soleus. Exercise down-regulated in the M. soleus in both strains, in the M. gastrocnemius only in normotensives. In SHRs exercise downregulated the expression of in the M. soleus. Exercise increased the expression of in the M. gastrocnemius in both strains, and that of GLUT-4 protein in the M. soleus, whereas it increased the muscle-specific expression of PCSK9 only in normotensive rats. Effects of exercise on the hepatic expression of cholesterol transporters were seen only in SHRs. As an acute response to exercise increased expressions of the myokine and that of were found in the muscles. This study, based on transcriptional adaptations in striated muscles and livers, shows that rats perform long-term metabolic adaptations when kept with increased physical activity. These adaptations are at least in part required to stabilize normal protein expression as protein turnover seems to be modified by exercise. However, normotensive and hypertensive rats differed in their responsiveness. Based on these results, a direct translation from normotensive to hypertensive rats is not possible. As genetic differences between normotensive humans and patients with essential hypertension are likely to be present as well, we would expect similar differences in humans that may impact recommendations for non-pharmacological interventions.
肥胖和高血压是心血管疾病的常见风险因素，而积极的生活方式被认为具有保护作用。然而，高强度体育活动与高血压之间的相互作用尚不清楚。因此，本研究调查了高强度体育活动对自发性高血压大鼠（SHR）肌肉和肝脏中葡萄糖转运蛋白（Glut）、解偶联蛋白（UCPs）和前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK9）表达的影响。24只雌性大鼠（12只血压正常大鼠和12只SHR）被分为久坐对照组和运动组，运动组大鼠在夜间可自由使用跑步轮，持续10个月。采集血样并测定血压。对内脏脂肪量进行半定量分析，然后切除腓肠肌、比目鱼肌和肝脏。对15只雌性SHR进行分析，在其自由使用跑步轮2天后处死，以分析自由跑步轮活动的急性影响。腓肠肌和比目鱼肌在 、 、 和 的mRNA表达上存在差异。高血压与腓肠肌中 和 mRNA水平较低相关，但与比目鱼肌中 和 表达增加相关。运动下调了两种品系比目鱼肌中的 ，仅下调了血压正常大鼠腓肠肌中的 。在SHR中，运动下调了比目鱼肌中 的表达。运动增加了两种品系腓肠肌中 的表达，以及比目鱼肌中GLUT - 4蛋白的表达，而仅在血压正常大鼠中增加了肌肉特异性PCSK9的表达。运动对肝脏胆固醇转运蛋白表达的影响仅在SHR中可见。作为对运动的急性反应，在肌肉中发现肌动蛋白 和 的表达增加。本研究基于横纹肌和肝脏中的转录适应性变化，表明大鼠在保持高强度体育活动时会进行长期的代谢适应性变化。这些适应性变化至少部分是为了稳定正常的蛋白质表达，因为蛋白质周转似乎因运动而改变。然而，血压正常和高血压大鼠的反应性不同。基于这些结果，无法直接将血压正常大鼠的情况类推到高血压大鼠。由于血压正常的人和原发性高血压患者之间可能也存在基因差异，我们预计人类也会有类似的差异，这可能会影响非药物干预的建议。
