Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland.
Clin Exp Pharmacol Physiol. 2021 Apr;48(4):585-596. doi: 10.1111/1440-1681.13451. Epub 2020 Dec 22.
This study examined the effect of leptin and orexin-A on autonomic baroreflex control in conscious Wistar rats exposed to high-fat (45% fat) or normal (3.4%) diet for 4 weeks. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were monitored during the generation of baroreflex gain curves and acute volume expansion (VEP). Intracerebroventricular (ICV) leptin (1 μg/min) increased RSNA in the normal diet group (0.31 ± 0.04 vs 0.23 ± 0.03 mV/s) and MAP in the high-fat diet group (115 ± 5 vs 105 ± 5 mm Hg, P < .05). Orexin-A (50 ng/min) increased RSNA, HR and MAP in the high-fat diet group (0.26 ± 0.03 vs 0.22 ± 0.02 mV/s, 454 ± 8 vs 417 ± 12 beats/min, 117 ± 1 vs 108 ± 1 mm Hg) and the normal diet group (0.18 ± 0.05 vs 0.17 ± 0.05 mV/s, 465 ± 10 vs 426 ± 6 beats/min, 116 ± 2 vs 104 ± 3 mm Hg). Baroreflex sensitivity for RSNA was increased during ICV leptin by 50% in the normal diet group, compared to 14% in the high-fat diet group (P < .05). Similarly, orexin-A increased baroreflex sensitivity by 56% and 50% in the high-fat and normal diet groups, respectively (all P < .05). During ICV saline, VEP decreased RSNA by 31 ± 5% (P < .05) after 10 minutes and the magnitude of this response was blunted during ICV infusion of leptin (17 ± 2%, P < .05) but not orexin-A in the normal diet group. RSNA response to VEP was not changed during ICV leptin or orexin-A in the high-fat diet group. These findings indicate possible central roles for leptin and orexin-A in modulating the baroreflexes under normal or increased fat intake in conscious rats and potential therapeutic approaches for obesity associated hypertension.
这项研究旨在探讨瘦素和食欲素-A 对暴露于高脂肪（45%脂肪）或正常（3.4%）饮食 4 周的清醒 Wistar 大鼠自主血压反射控制的影响。在产生血压反射增益曲线和急性容量扩张（VEP）期间，监测肾交感神经活动（RSNA）、平均动脉压（MAP）和心率（HR）。脑室注射（ICV）瘦素（1μg/min）增加了正常饮食组的 RSNA（0.31±0.04 对 0.23±0.03 mV/s）和 MAP（115±5 对 105±5 mmHg，P<.05）。食欲素-A（50ng/min）增加了高脂肪饮食组的 RSNA、HR 和 MAP（0.26±0.03 对 0.22±0.02 mV/s，454±8 对 417±12 次/分钟，117±1 对 108±1 mmHg）和正常饮食组（0.18±0.05 对 0.17±0.05 mV/s，465±10 对 426±6 次/分钟，116±2 对 104±3 mmHg）。与高脂肪饮食组的 14%相比，脑室注射瘦素使正常饮食组的 RSNA 血压反射敏感性增加了 50%（P<.05）。同样，食欲素-A 使高脂肪和正常饮食组的血压反射敏感性分别增加了 56%和 50%（均 P<.05）。在脑室注射盐水期间，VEP 在 10 分钟后使 RSNA 降低了 31±5%（P<.05），而在正常饮食组中，脑室注射瘦素后，这种反应的幅度降低了 17±2%（P<.05），但在脑室注射食欲素-A 时则没有降低。在高脂肪饮食组中，脑室注射瘦素或食欲素-A 并未改变 RSNA 对 VEP 的反应。这些发现表明，瘦素和食欲素-A 在调节清醒大鼠在正常或增加脂肪摄入下的血压反射方面可能发挥中枢作用，并且为肥胖相关高血压提供了潜在的治疗方法。
