RESUMEN
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.