Abstract：
The aim of this study is to verify the impact of Leptin in blood pressure (BP) regulation and Leptin-resistance in metabolic/neurogenic hypertension through baroreflex afferents and dysregulation. Artery BP/heart rate (HR) were measured while nodose (NG) microinjection of Leptin, membrane depolarization/inward current were obtained by whole-cell patch from NG neurons isolated from adult female rats. Baroreflex sensitivity (BRS) tested with PE/SNP, distribution/expression of Leptin/receptors in the NG/nucleus tractus solitary (NTS) examined using immumostaining and qRT-PCR, and serum concentrations of Leptin/NE measured by ELISA were observed in control and high fructose-drinking induced hypertension (HTN-HFD) rats. The results showed that BP was significantly/dose-dependently reduced by Leptin NG microinjection likely through direct excitation of female-specific subpopulation of Ah-type neurons showing a potent membrane depolarization/inward currents. Sex-specific distribution/expression of OB-Ra/OB-Rb in the NG were detected with estrogen-dependent manner, similar observations were also confirmed in the NTS. As expected, BRS was dramatically decreased in the presence of PE/SNP in both male and female rats except for the female with PE at given concentrations. Additionally, serum concentration of Leptin was elevated in HFD-HTN model rats of either sex with more obvious in females. Under hypertensive condition, the mean fluorescent density of OB-R and mRNA expression for OB-Ra/OB-Rb in the NG/NTS were significantly down-regulated. These results have demonstrated that Leptin play a role in dominant parasympathetic drive via baroreflex afferent activation to buffer Leptin-mediated sympathetic activation systemically and Leptin-resistance is an innegligible mechanism for metabolic/neurogenic hypertension through baroreflex afferent dysregulation.
摘要：
这项研究的目的是通过压力反射传入和失调来验证瘦素在血压（BP）调节和瘦素抵抗在代谢/神经源性高血压中的影响。测量动脉BP/心率（HR），同时不注射（NG）微量注射瘦素，通过从成年雌性大鼠分离的NG神经元的全细胞贴片获得膜去极化/内向电流。用PE/SNP测试的压力反射灵敏度（BRS），使用免疫染色和qRT-PCR检查NG/孤立核束（NTS）中瘦素/受体的分布/表达，用ELISA法测定对照组和高果糖饮酒诱导的高血压（HTN-HFD）大鼠的血清瘦素/NE浓度。结果表明，通过LeptinNG显微注射，BP显着/剂量依赖性地降低，可能是通过直接激发Ah型神经元的女性特异性亚群，显示出有效的膜去极化/内向电流。以雌激素依赖性方式检测NG中OB-Ra/OB-Rb的性别特异性分布/表达。在NTS中也证实了类似的观察结果.不出所料,在雄性和雌性大鼠中,在存在PE/SNP的情况下,BRS显著降低,除了具有给定浓度的PE的雌性大鼠。此外,任一性别的HFD-HTN模型大鼠血清瘦素浓度均升高，雌性更为明显。在高血压状态下，NG/NTS中OB-R的平均荧光密度和OB-Ra/OB-Rb的mRNA表达显著下调。这些结果表明，瘦素通过压力反射传入激活在主要的副交感神经驱动中起作用，以系统地缓冲瘦素介导的交感神经激活，而瘦素抵抗是通过压力反射传入失调进行代谢/神经源性高血压的不可忽视的机制。
