Effect of centrally acting angiotensin converting enzyme inhibitor on the exercise-induced increases in muscle sympathetic nerve activity

Gilbert Moralez, Noah P. Jouett, Jun Tian, Matthew C. Zimmerman, Paul Bhella, Peter B. Raven

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Key points: The arterial baroreflex's operating point pressure is reset upwards and rightwards from rest in direct relation to the increases in dynamic exercise intensity. The intraneural pathways and signalling mechanisms that lead to upwards and rightwards resetting of the operating point pressure, and hence the increases in central sympathetic outflow during exercise, remain to be identified. We tested the hypothesis that the central production of angiotensin II during dynamic exercise mediates the increases in sympathetic outflow and, therefore, the arterial baroreflex operating point pressure resetting during acute and prolonged dynamic exercise. The results identify that perindopril, a centrally acting angiotensin converting enzyme inhibitor, markedly attenuates the central sympathetic outflow during acute and prolonged dynamic exercise. Abstract: We tested the hypothesis that the signalling mechanisms associated with the dynamic exercise intensity related increases in muscle sympathetic nerve activity (MSNA) and arterial baroreflex resetting during exercise are located within the central nervous system. Participants performed three randomly ordered trials of 70° upright back-supported dynamic leg cycling after ingestion of placebo and two different lipid soluble angiotensin converting enzyme inhibitors (ACEi): perindopril (high lipid solubility), captopril (low lipid solubility). Repeated measurements of whole venous blood (n = 8), MSNA (n = 7) and arterial blood pressures (n = 14) were obtained at rest and during an acute (SS1) and prolonged (SS2) bout of steady state dynamic exercise. Arterial baroreflex function curves were modelled at rest and during exercise. Peripheral venous superoxide concentrations measured by electron spin resonance spectroscopy were elevated during exercise and were not altered by ACEi at rest (P ≥ 0.4) or during exercise (P ≥ 0.3). Baseline MSNA and mean arterial pressure were unchanged at rest (P ≥ 0.1; P ≥ 0.8, respectively). However, during both SS1 and SS2, the centrally acting ACEi perindopril attenuated MSNA compared to captopril and the placebo (P < 0.05). Arterial pressures at the operating point and threshold pressures were decreased with perindopril from baseline to SS1 with no further changes in the operating point pressure during SS2 under all three conditions. These data suggest that centrally acting ACEi is significantly more effective at attenuating the increase in the acute and prolonged exercise-induced increases in MSNA.

Original languageEnglish (US)
Pages (from-to)2315-2332
Number of pages18
JournalJournal of Physiology
Volume596
Issue number12
DOIs
StatePublished - Jun 15 2018

Keywords

  • Angiotensin II
  • Electron Spin Resonance
  • Free Radicals
  • Functional Sympatholysis
  • Muscle Sympathetic Nerve Activity
  • Nitric Oxide
  • Superoxide

ASJC Scopus subject areas

  • Physiology

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