Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats

The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280–350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50–60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation.

本研究旨在探究血管紧张素转换酶2（angiotensin converting enzyme 2，ACE2）激活剂醋酸二脒那嗪（diminazene aceturate，DIZE）联合有氧训练对自发性高血压大鼠（spontaneously hypertensive rats，SHRs）的心血管效应。选取体重280~350 g的雄性自发性高血压大鼠，分为运动训练组与安静对照组。运动训练组接受为期8周的跑台有氧训练：每周训练5次，每次训练时长60 min，运动强度为最大有氧速度的50%~60%。
在实验方案的最后15天，将所有大鼠重新分为4组：① 每日予以1 mg/kg醋酸二脒那嗪的安静高血压大鼠组（S+D1）；② 每日予以1 mg/kg醋酸二脒那嗪的运动训练高血压大鼠组（T+D1）；③ 每日予以溶剂对照的安静高血压大鼠组（S+V）；④ 每日予以溶剂对照的运动训练高血压大鼠组（T+V）。
干预结束后，对大鼠实施麻醉，进行动脉与股静脉插管，并植入心电图（electrocardiogram，ECG）电极。24 h后，记录平均动脉压（mean arterial pressure，MAP）与心率（heart rate，HR）；在非麻醉状态下评估压力感受性反射敏感性以及双重自主神经阻滞（double autonomic blockade，DAB）的效应。
相较于T+V组与S+D1组，T+D1组的压力感受性反射敏感性得到显著改善；同时，T+D1组的固有心率（intrinsic heart rate，IHR）与平均动脉压均低于T+V组与S+D1组。
综上，本研究表明，有氧训练联合醋酸二脒那嗪治疗可改善自发性高血压大鼠的压力感受性反射功能与心血管调控能力。