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_B) receptor activation on adrenergic nerves decreases baroreflex sensitivity. We utilized male ET_B receptor deficient (ET_B-def) rats that express functional ET_B 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_B-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_B-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_B receptor antagonist, A-192621 (10 mg/kg/day), to block ET_B receptors. Following ET_B 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_B receptors on adrenergic nerves contribute to baroreflex dysfunction.

压力感受反射功能是维持血压稳定的重要组成部分。高血压通常与压力反射功能障碍有关，而高盐饮食等环境危险因素会加剧压力反射功能障碍患者的高血压。然而，高盐饮食、压力反射功能障碍和高血压之间的相互作用尚不完全清楚。内皮素系统是血压控制的另一种有效介质，尤其是对高盐饮食的反应。我们假设肾上腺素能神经上的内皮素 B (ET _B ) 受体激活会降低压力反射敏感性。我们利用仅在肾上腺素能神经上表达功能性 ET _{B受体的雄性 ET B}受体缺陷 (ET _B -def) 大鼠和转基因 (TG) 对照来评估正常 (0.49% 氯化钠) 和高盐 (4.0% 氯化钠) 饮食期间的压力反射功能。在配备遥测技术的清醒大鼠中，与 TG 对照相比，ET _B -def 大鼠的收缩压 (SBP) 不稳定性增加，如正常条件下 SBP 较高的标准差 (SD) 所示（10.2 ± 0.6 与 12.4 ± 0.9）分别为毫米汞柱，p  = 0.0001）和高盐饮食（11.7 ± 0.6 与 16.1 ± 1.0 毫米汞柱，p = 0.0001）。在麻醉制剂中，ET _B -def 大鼠表现出心率（p 基因型 = 0.0167）和肾交感神经（p 基因型 = 0.0022）压力反射敏感性降低。然后，我们给雄性 Sprague-Dawley 大鼠注射选择性 ET _B受体拮抗剂 A-192621（10 毫克/公斤/天），以阻断 ET _B受体。ET _B受体拮抗后，即使 SBP 升高（之前 131 ± 7 vs. 152 ± 8 mmHg，p  < 0.0001），SBP 的不稳定性（标准差）却下降（9.3 ± 2.0 vs. 7.1 ± 1.1 mmHg，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 _B受体导致压力反射功能障碍。