Department of Physiology, Campus São Paulo, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Department of Biological Sciences, Campus Diadema, Universidade Federal de São Paulo, São Paulo, Brazil.
Hypertens Res. 2019 Nov;42(11):1683-1691. doi: 10.1038/s41440-019-0301-z. Epub 2019 Jul 17.
Sympathetic overactivation contributes to the pathogenesis of both experimental and human hypertension. We have previously reported that oxidative stress in sympathetic premotor neurons leads to arterial baroreflex dysfunction and increased sympathetic drive to the kidneys in an experimental model of neurogenic hypertension. In this study, we hypothesized that melatonin, a potent antioxidant, may be protective in the brainstem regions involved in the tonic and reflex control of blood pressure (BP) in renovascular hypertensive rats. Neurogenic hypertension was induced by placing a silver clip (gap of 0.2 mm) around the left renal artery, and after 5 weeks of renal clip placement, the rats were treated orally with melatonin (30 mg/kg/day) by gavage for 15 days. At the end of melatonin treatment, we evaluated baseline mean arterial pressure (MAP), renal sympathetic nerve activity (rSNA), and the baroreflex control of heart rate (HR) and rSNA. Reactive oxygen species (ROS) were detected within the brainstem regions by dihydroethidium staining. Melatonin treatment effectively reduced baseline MAP and sympathoexcitation to the ischemic kidney in renovascular hypertensive rats. The baroreflex control of HR and rSNA were improved after melatonin treatment in the hypertensive group. Moreover, there was a preferential decrease in ROS within the rostral ventrolateral medulla (RVLM) and the nucleus of the solitary tract (NTS). Therefore, our study indicates that melatonin is effective in reducing renal sympathetic overactivity associated with decreased ROS in brainstem regions that regulate BP in an experimental model of neurogenic hypertension.
交感神经过度激活参与了实验性和人类高血压的发病机制。我们之前曾报道过，交感节前神经元中的氧化应激会导致动脉压力反射功能障碍，并增加神经源性高血压实验模型中肾脏的交感神经驱动。在这项研究中，我们假设褪黑素作为一种有效的抗氧化剂，可能对参与血压（BP）紧张性和反射性调节的脑干区域具有保护作用。通过在左肾动脉周围放置银夹（间隙 0.2mm）来诱导神经源性高血压，在肾夹放置 5 周后，通过灌胃给予大鼠褪黑素（30mg/kg/天）治疗 15 天。在褪黑素治疗结束时，我们评估了基础平均动脉压（MAP）、肾交感神经活动（rSNA）以及心率（HR）和 rSNA 的压力反射控制。通过二氢乙啶染色检测脑干区域内的活性氧物质（ROS）。褪黑素治疗可有效降低肾血管性高血压大鼠的基础 MAP 和对缺血侧肾脏的交感神经兴奋。在高血压组中，褪黑素治疗后 HR 和 rSNA 的压力反射控制得到改善。此外，在 RVLM 和孤束核（NTS）内，ROS 优先减少。因此，我们的研究表明，褪黑素在降低与 BP 调节相关的脑干区域中与 ROS 减少相关的肾交感神经过度活动方面是有效的，这是神经源性高血压的实验模型。
