Pediatric Department, Shanghai General Hospital, Shanghai, China.
Department of Cardiothoracic Surgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Neuropeptides. 2020 Apr;80:102021. doi: 10.1016/j.npep.2020.102021. Epub 2020 Jan 20.
Neuropeptides are involved in the regulation of the sympathetic activity and blood pressure in the paraventricular nucleus of the hypothalamus (PVN). The present study was designed to determine how alarin modulates the renal sympathetic nerve activity (RSNA), arterial blood pressure and mean arterial pressure (MAP) in the PVN, and whether superoxide anions regulate the effects of alarin in the PVN of spontaneously hypertensive rats (SHRs). Acute experiment was carried out with male Wistar-Kyoto rats (WKY) and SHRs under anesthesia. RSNA, systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP were measured. Alarin microinjection into the PVN increased RSNA (7.8 ± 1.8 vs. 14.8 ± 2.3%), SBP (5.9 ± 1.4 vs. 12.1 ± 1.6 mmHg), DBP (5.1 ± 0.8 vs. 10.0 ± 1.1 mmHg), and MAP (5.4 ± 1.2 vs. 10.7 ± 1.3 mmHg) in WKY rats and SHRs,. Alarin antagonist ala6-25 Cys decreased RSNA, SBP, DBP, and MAP in SHRs, and inhibited the effects of alarin. The alarin level was increased in the PVN of SHR compared to WKY rats. (29.7 ± 4.9 vs. 14.6 ± 2.4 pg/mg protein). PVN microinjection of superoxide anion scavengers tempol and tiron, or NAD(P)H oxidase inhibitor apocynin, decreased RSNA, SBP, DBP, and MAP in SHRs, and inhibited the effects of alarin, but the superoxide dismutase inhibitor diethyldithiocarbamic acid potentiated the effects of alarin. Superoxide anions and NAD(P)H oxidase activity levels in the PVN were increased by alarin, but decreased by alarin antagonist ala6-25 Cys. The alarin-induced increases in superoxide anions and NAD(P)H oxidase activity levels were abolished by pre-treatment with ala6-25 Cys. The results suggest that alarin in the PVN increases sympathetic outflow and blood pressure. The enhanced activity of endogenous alarin in the PVN contributes to sympathetic activation in hypertension, and the superoxide anion is involved in these alarin-mediated processes in the PVN.
神经肽参与下丘脑室旁核 (PVN) 交感活动和血压的调节。本研究旨在确定阿拉林如何调节肾交感神经活动 (RSNA)、动脉血压和平均动脉压 (MAP) 在 PVN 中，以及超氧阴离子是否调节阿拉林在自发性高血压大鼠 (SHR) 的 PVN 中的作用。急性实验在麻醉下进行雄性 Wistar-Kyoto 大鼠 (WKY) 和 SHR。测量 RSNA、收缩压 (SBP)、舒张压 (DBP) 和 MAP。阿拉林微注射到 PVN 增加了 WKY 大鼠和 SHR 的 RSNA（7.8±1.8%对 14.8±2.3%）、SBP（5.9±1.4%对 12.1±1.6mmHg）、DBP（5.1±0.8%对 10.0±1.1mmHg）和 MAP（5.4±1.2%对 10.7±1.3mmHg）。阿拉林拮抗剂 ala6-25 Cys 降低了 SHR 的 RSNA、SBP、DBP 和 MAP，并抑制了阿拉林的作用。与 WKY 大鼠相比，SHR 的 PVN 中阿拉林水平升高。（29.7±4.9 对 14.6±2.4pg/mg 蛋白）。PVN 微注射超氧阴离子清除剂 tempol 和 tiron 或 NAD(P)H 氧化酶抑制剂 apocynin 降低了 SHR 的 RSNA、SBP、DBP 和 MAP，并抑制了阿拉林的作用，但超氧化物歧化酶抑制剂二乙基二硫代氨基甲酸钠增强了阿拉林的作用。超氧阴离子和 NAD(P)H 氧化酶活性水平在 PVN 中被阿拉林增加，但被阿拉林拮抗剂 ala6-25 Cys 降低。阿拉林诱导的超氧阴离子和 NAD(P)H 氧化酶活性水平的增加被 ala6-25 Cys 预处理所消除。结果表明，PVN 中的阿拉林增加了交感神经输出和血压。PVN 中内源性阿拉林活性的增强有助于高血压中的交感神经激活，超氧阴离子参与了这些 PVN 中介过程。
