Ruchaya Prashant J, Speretta Guilherme F, Blanch Graziela Torres, Li Hongwei, Sumners Colin, Menani José V, Colombari Eduardo, Colombari Débora S A
Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, SP, Brazil.
School of Biotechnology, Southern Medical University, Guangzhou, China.
Neuropeptides. 2016 Dec;60:29-36. doi: 10.1016/j.npep.2016.06.006. Epub 2016 Jul 20.
The aim of this study was to investigate the physiological effects of increased angiotensin II type 2 receptor (AT2R) expression in the solitary-vagal complex (nucleus of the solitary tract/dorsal motor nucleus of the vagus; NTS/DVM) on baroreflex function in non-anaesthetised normotensive (NT) and spontaneously hypertensive rats (SHR). Ten week old NT Holtzman and SHR were microinjected with either an adeno-associated virus expressing AT2R (AAV2-CBA-AT2R) or enhanced green fluorescent protein (control; AAV2-CBA-eGFP) into the NTS/DVM. Baroreflex and telemetry recordings were performed on four experimental groups: 1) NTeGFP, 2) NTAT2R, 3) SHReGFP and 4) SHRAT2R (n=4-7/group). Following in-vivo experimental procedures, brains were harvested for gene expression analysis. Impaired bradycardia in SHReGFP was restored in SHR rats overexpressing AT2R in the NTS/DMV. mRNA levels of angiotensin converting enzyme decreased and angiotensin converting enzyme 2 increased in the NTS/DMV of SHRAT2R compared to SHReGFP. Increased levels of pro-inflammatory cytokine mRNA levels in the SHReGFP group also decreased in the SHRAT2R group. AT2R overexpression did not elicit any significant change in mean arterial pressure (MAP) in all groups from baseline to 4weeks post viral transfection. Both SHReGFP and SHRAT2R showed a significant elevation in MAP compared to the NTeGFP and NTAT2R groups. Increased AT2R expression within the NTS/DMV of SHR was effective at improving baroreflex function but not MAP. We propose possible mediators involved in improving baroreflex are in the ANG II/ACE2 axis, suggesting a potential beneficial modulatory effect of AT2R overexpression in the NTS/DMV of neurogenic hypertensive rats.
本研究的目的是调查孤束核/迷走神经背运动核（NTS/DVM）中血管紧张素II 2型受体（AT2R）表达增加对未麻醉的正常血压（NT）大鼠和自发性高血压大鼠（SHR）压力反射功能的生理影响。将表达AT2R的腺相关病毒（AAV2-CBA-AT2R）或增强型绿色荧光蛋白（对照；AAV2-CBA-eGFP）显微注射到10周龄的NT霍尔兹曼大鼠和SHR的NTS/DVM中。对四个实验组进行压力反射和遥测记录：1）NT eGFP，2）NT AT2R，3）SHR eGFP和4）SHR AT2R（每组n = 4 - 7）。在体内实验程序完成后，收获大脑进行基因表达分析。在NTS/DMV中过表达AT2R的SHR大鼠恢复了SHR eGFP中受损的心动过缓。与SHR eGFP相比，SHR AT2R的NTS/DMV中血管紧张素转换酶的mRNA水平降低，血管紧张素转换酶2增加。SHR AT2R组中SHR eGFP组促炎细胞因子mRNA水平的升高也降低了。从基线到病毒转染后4周，AT2R过表达在所有组中均未引起平均动脉压（MAP）的任何显著变化。与NT eGFP和NT AT2R组相比，SHR eGFP和SHR AT2R的MAP均显著升高。SHR的NTS/DMV内AT2R表达增加可有效改善压力反射功能，但不能改善MAP。我们提出参与改善压力反射的可能介质存在于ANG II/ACE2轴中，这表明AT2R在神经源性高血压大鼠的NTS/DMV中过表达具有潜在的有益调节作用。
