Superoxide anions mediate the effects of angiotensin (1-7) analog, alamandine, on blood pressure and sympathetic activity in the paraventricular nucleus

Juexiao Gong, Yihui Shen, Peng Li, Kun Zhao, Xuguan Chen, Yong Li, Yanhui Sheng, Bin Zhou, Xiangqing Kong

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Microinjection of alamandine into the hypothalamic paraventricular nucleus (PVN) increased blood pressure and enhanced sympathetic activity. The aim of this study was to determine if superoxide anions modulate alamandine's effects in the PVN. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were recorded in anaesthetized normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Microinjection of alamandine into the PVN increased MAP and RSNA in both WKY rats and SHRs, although to a greater extent in SHRs. These effects were blocked by pretreatment with an alamandine receptor (MrgD) antagonist D-Pro7-Ang-(1–7). Pretreatment with superoxide anion scavengers, tempol and tiron, and NADPH oxidase inhibitor apocynin (APO), also blocked the effects of alamandine on MAP and RSNA. In addition, pretreatment in the PVN with a superoxide dismutase (SOD) inhibitor diethyldithiocarbamic acid (DETC) potentiated the increases of MAP and RSNA induced by alamandine administration, with a greater response observed in SHRs. Superoxide anions and NADPH oxidase levels in the PVN were higher in SHRs than that in WKY rats. Alamandine treatment increased the levels of superoxide anions and NADPH oxidase in WKY and SHRs, however, with greater effect in SHRs. These alamandine-induced increases were inhibited by D-Pro7-Ang-(1–7) pretreatment in the PVN of both rats. These results demonstrate that superoxide anions in the PVN modulate alamandine-induced increases in blood pressure and sympathetic activity in both normotensive and hypertensive rats. Alamandine increases NADPH oxidase activity to induce superoxide anion production, which is mediated by the alamandine receptor.

Original languageEnglish (US)
Article number170101
StatePublished - Aug 2019
Externally publishedYes


  • Alamandine
  • NADPH oxidase
  • Paraventricular nucleus
  • Spontaneously hypertensive rat
  • Superoxide anion

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience


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