Department of Physiology, The Fourth Military Medical University, Xi'an, China;
Am J Physiol Heart Circ Physiol. 2013 Oct 15;305(8):H1111-9. doi: 10.1152/ajpheart.00290.2013. Epub 2013 Aug 2.
Exercise training lowers blood pressure and is a recommended nonpharmacological strategy and useful adjunctive therapy for hypertensive patients. Studies demonstrate that physical activity attenuates progression of hypertension. However, underlying mechanisms remain elusive. Vascular insulin resistance and endothelial dysfunction plays a critical role in the development of hypertension. The present study investigated whether long-term physical exercise starting during the prehypertensive period prevents the development of hypertension via improving vascular insulin sensitivity. Young (4 wk old) prehypertensive spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto (WKY) control rats were subjected to a 10-wk free-of-loading swim training session (60 min/day, 5 days/wk). Blood pressure, mesenteric arteriolar vasorelaxation, G protein-coupled receptor kinase-2 (GRK2) expression and activity, and insulin-stimulated Akt/endothelial nitric oxide synthase (eNOS) activation were determined. SHRs had higher systolic blood pressure, systemic insulin resistance, and impaired vasodilator actions of insulin in resistance vessels when compared with WKY rats. Systolic blood pressure in SHRs postexercise was significantly lower than that in sedentary rats. Vascular insulin sensitivity in mesenteric arteries was improved after exercise training as evidenced by an increased vasodilator response to insulin. In addition, exercise downregulated vascular GRK2 expression and activity, which further increased insulin-stimulated vascular Akt/eNOS activation in exercised SHRs. Specific small interfering RNA knockdown of GRK2 in endothelium mimicked the effect of exercise-enhanced vascular insulin sensitivity. Likewise, upregulation of GRK2 by Chariot-mediated delivery opposed exercise-induced vascular insulin sensitization. Taken together, our results suggest that long-term exercise beginning at the prehypertensive stage improves vascular insulin sensitivity via downregulation of vascular GRK2 that may help to limit the progression of hypertension.
运动训练可降低血压，是高血压患者推荐的非药物治疗策略和有用的辅助治疗方法。研究表明，体力活动可减缓高血压的进展。然而，其潜在机制仍不清楚。血管胰岛素抵抗和内皮功能障碍在高血压的发展中起着关键作用。本研究探讨了长期的运动训练是否可以通过改善血管胰岛素敏感性来预防高血压前期高血压的发展。将年轻（4 周龄）的自发性高血压大鼠（SHR）和其正常血压的 Wistar-Kyoto（WKY）对照大鼠进行 10 周的无负重游泳训练（60 分钟/天，每周 5 天）。测定血压、肠系膜小动脉血管舒张、G 蛋白偶联受体激酶-2（GRK2）表达和活性以及胰岛素刺激的 Akt/内皮型一氧化氮合酶（eNOS）激活。与 WKY 大鼠相比，SHR 大鼠的收缩压更高、全身胰岛素抵抗和阻力血管中胰岛素的血管舒张作用受损。与久坐不动的 SHR 相比，运动后的 SHR 收缩压明显降低。运动训练后肠系膜动脉的血管胰岛素敏感性得到改善，表现为对胰岛素的血管舒张反应增加。此外，运动可下调血管 GRK2 的表达和活性，这进一步增加了运动后的 SHR 中胰岛素刺激的血管 Akt/eNOS 激活。内皮细胞中 GRK2 的特异性小干扰 RNA 敲低模拟了运动增强血管胰岛素敏感性的作用。同样，通过 Chariot 介导的递送上调 GRK2 会阻碍运动引起的血管胰岛素敏感性。综上所述，我们的研究结果表明，在高血压前期开始进行长期运动可以通过下调血管 GRK2 来改善血管胰岛素敏感性，这可能有助于限制高血压的进展。
