ACE2 gene combined with exercise training attenuates central AngII/AT1 axis function and oxidative stress in a prehypertensive rat model

Xiu Yun Chen, Cheng Lin, Guo Ying Liu, Chun Pei, Gui Qing Xu, Lie Gao, Shi Zhong Wang, Yan Xia Pan

Research output: Contribution to journalArticlepeer-review

Abstract

Angiotensin-converting enzyme 2 (ACE2) or exercise training (ExT) is beneficial to hypertension, but their combined effects remain unknown. In this study, lentivirus containing enhanced green fluorescent protein (eGFP) and ACE2 were microinjected into the paraventricular nucleus (PVN) of young male spontaneous hypertensive rats (SHRs), and SHRs were assigned into five groups: sedentary (SHR), SHR-ExT, SHR-eGFP, ACE2 gene (SHR-ACE2), and ACE2 gene combined with ExT (SHR-ACE2-ExT). Wistar–Kyoto (WKY) rats were used as a control. ACE2 gene or ExT significantly delayed the elevation of blood pressure, and the combined effect prevented the development and progression of prehypertension. Either ACE2 overexpression or ExT improved arterial baroreflex sensitivity (BRS), whereas the combined effect normalized BRS in SHR. Compared with SHR, SHR-ACE2 and SHR-ExT displayed a significantly higher level of ACE2 protein but had lower plasma norepinephrine (NE) and angiotensin II (AngII) as well as angiotensin II type 1 receptor (AT1) protein expression in the PVN. SHR-ACE2-ExT showed the largest decrease in AngII and AT1 protein expression. Reactive oxygen species (ROS) level and NADPH oxidase (NOX2 and NOX4) protein expression in PVN were also decreased in SHR-ACE2-ExT group than in SHR-ACE2 and SHR-ExT groups. It was concluded that the combined effect has effectively prevented prehypertension progression and baroreflex dysfunction in SHR, which is associated with the reduction in AngII/AT1 axis function and oxidative stress in the PVN.

Original languageEnglish (US)
Pages (from-to)1460-1467
Number of pages8
JournalJournal of Applied Physiology
Volume132
Issue number6
DOIs
StatePublished - Jun 2022

Keywords

  • baroreflex
  • exercise training
  • hypertension
  • paraventricular nucleus
  • renin-angiotensin system

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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