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Superoxide anions modulate the effects of alarin in the paraventricular nucleus on sympathetic activity and blood pressure in spontaneously hypertensive rats
Neuropeptides ( IF 2.5 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.npep.2020.102021
Qian Wang 1 , Fanxin Deng 2 , Dawei Zhu 2
Affiliation  

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.

中文翻译:

超氧阴离子调节室旁核阿拉林对自发性高血压大鼠交感神经活动和血压的影响

神经肽参与调节下丘脑室旁核 (PVN) 的交感神经活动和血压。本研究旨在确定 alarin 如何调节 PVN 中的肾交感神经活动 (RSNA)、动脉血压和平均动脉压 (MAP),以及超氧阴离子是否调节 alarin 在自发性高血压大鼠的 PVN 中的作用。 SHR)。在麻醉下用雄性 Wistar-Kyoto 大鼠 (WKY) 和 SHR 进行急性实验。测量了 RSNA、收缩压 (SBP)、舒张压 (DBP) 和 MAP。将 Alarin 显微注射到 PVN 增加了 RSNA(7.8 ± 1.8 与 14.8 ± 2.3%)、SBP(5.9 ± 1.4 与 12.1 ± 1.6 mmHg)、DBP(5.1 ± 0.8 与 10.0 ± 1.1 mmHg)和 ±4(5 1.2 与 10.7 ± 1.3 mmHg) 在 WKY 大鼠和 SHR 中。Alarin 拮抗剂 ala6-25 Cys 降低了 SHR 中的 RSNA、SBP、DBP 和 MAP,并抑制了 alarin 的作用。与 WKY 大鼠相比,SHR 的 PVN 中的 alarin 水平增加。(29.7 ± 4.9 与 14.6 ± 2.4 pg/mg 蛋白质)。PVN 显微注射超氧阴离子清除剂 tempol 和 tiron,或 NAD(P)H 氧化酶抑制剂夹竹桃麻素,降低 SHR 中的 RSNA、SBP、DBP 和 MAP,并抑制 alarin 的作用,但超氧化物歧化酶抑制剂二乙基二硫代氨基甲酸增强了阿拉林。PVN 中的超氧阴离子和 NAD(P)H 氧化酶活性水平被 alarin 增加,但被 alarin 拮抗剂 ala6-25 Cys 降低。通过用 ala6-25 Cys 预处理可以消除 alarin 诱导的超氧阴离子和 NAD(P)H 氧化酶活性水平的增加。结果表明 PVN 中的 alarin 增加了交感神经流出和血压。PVN 中内源性 alarin 的活性增强有助于高血压的交感神经激活,超氧阴离子参与 PVN 中这些 alarin 介导的过程。
更新日期:2020-04-01
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