Cardio-Renal Physiology and Medicine, Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35294, United States of America.
Cardio-Renal Physiology and Medicine, Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35294, United States of America.
Auton Neurosci. 2021 May;232:102796. doi: 10.1016/j.autneu.2021.102796. Epub 2021 Mar 11.
Baroreflex function is an integral component maintaining consistent blood pressure. Hypertension is often associated with baroreflex dysfunction, and environmental risk factors such as high salt diet exacerbate hypertension in subjects with baroreflex dysfunction. However, the interactions between high salt diet, baroreflex dysfunction, and hypertension are incompletely understood. The endothelin system is another potent mediator of blood pressure control especially in response to a high salt diet. We hypothesized that the endothelin B (ET) receptor activation on adrenergic nerves decreases baroreflex sensitivity. We utilized male ET receptor deficient (ET-def) rats that express functional ET receptors only on adrenergic nerves and transgenic (TG) controls to evaluate baroreflex function during normal (0.49% NaCl) and high (4.0% NaCl) salt diets. In conscious rats equipped with telemetry, ET-def rats had an increased lability of systolic blood pressure (SBP) compared to TG controls as indicated by higher standard deviation (SD) of SBP under both normal (10.2 ± 0.6 vs. 12.4 ± 0.9 mmHg, respectively, p = 0.0001) and high (11.7 ± 0.6 vs. 16.1 ± 1.0 mmHg, p = 0.0001) salt diets. In anesthetized preparations, ET-def rats displayed reduced heart rate (p genotype = 0.0167) and renal sympathetic nerve (p genotype = 0.0022) baroreflex sensitivity. We then gave male Sprague-Dawley rats the selective ET receptor antagonist, A-192621 (10 mg/kg/day), to block ET receptors. Following ET receptor antagonism, even though SBP increased (131 ± 7 before vs. 152 ± 8 mmHg after, p < 0.0001), the lability (standard deviation) of SBP decreased (9.3 ± 2.0 vs. 7.1 ± 1.1 mmHg, p = 0.0155). These data support our hypothesis that ET receptors on adrenergic nerves contribute to baroreflex dysfunction.
压力感受反射功能是维持血压稳定的一个重要组成部分。高血压常伴有压力感受反射功能障碍，而高盐饮食等环境危险因素可加重压力感受反射功能障碍患者的高血压。然而，高盐饮食、压力感受反射功能障碍和高血压之间的相互作用尚不完全清楚。内皮素系统是另一个强有力的血压控制介质，尤其是在高盐饮食时。我们假设肾上腺素能神经上的内皮素 B（ETB）受体激活会降低压力感受反射敏感性。我们利用仅在肾上腺素能神经上表达功能性 ET 受体的雄性 ET 受体缺陷（ET-def）大鼠和转基因（TG）对照来评估正常（0.49%NaCl）和高盐（4.0%NaCl）饮食期间的压力感受反射功能。在配备遥测设备的清醒大鼠中，与 TG 对照相比，ET-def 大鼠的收缩压（SBP）波动性增加，表现在正常（分别为 10.2 ± 0.6 与 12.4 ± 0.9mmHg，p = 0.0001）和高盐（分别为 11.7 ± 0.6 与 16.1 ± 1.0mmHg，p = 0.0001）饮食时 SBP 的标准差更高。在麻醉动物中，ET-def 大鼠的心率（p 基因型 = 0.0167）和肾交感神经（p 基因型 = 0.0022）压力感受反射敏感性降低。然后，我们给雄性 Sprague-Dawley 大鼠给予选择性 ET 受体拮抗剂 A-192621（10mg/kg/天）以阻断 ET 受体。在阻断 ET 受体后，尽管 SBP 升高（131 ± 7mmHg 与 152 ± 8mmHg，p < 0.0001），但 SBP 的波动性（标准差）降低（9.3 ± 2.0mmHg 与 7.1 ± 1.1mmHg，p = 0.0155）。这些数据支持我们的假设，即肾上腺素能神经上的 ET 受体有助于压力感受反射功能障碍。
