Central angiotensin (1-7) enhances baroreflex gain in conscious rabbits with heart failure

Sumit Kar, Lie Gao, Daniel A. Belatti, Pamela L. Curry, Irving H. Zucker

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

In chronic heart failure (CHF), arterial baroreflex function is impaired, in part, by activation of the central renin-angiotensin system. A metabolite of angiotensin (Ang) II, Ang-(1-7), has been shown to exhibit cardiovascular effects that are in opposition to that of Ang II. However, the action of Ang-(1-7) on sympathetic outflow and baroreflex function is not well understood, especially in CHF. The aim of this study was to determine the effect of intracerebroventricular infusion of Ang-(1-7) on baroreflex control of heart rate and renal sympathetic nerve activity in conscious rabbits with CHF. We hypothesized that central Ang-(1-7) would improve baroreflex function in CHF. Ang-(1-7) (2 nmol/1 μL per hour) or artificial cerebrospinal fluid (1 μL per hour) was infused by an osmotic minipump for 4 days in sham and pacing-induced CHF rabbits (n=3 to 6 per group). Ang-(1-7) treatment had no effects in sham rabbits but reduced heart rate and increased baroreflex gain (7.4±1.5 versus 2.5±0.4 bpm/mm Hg; P<0.05) in CHF rabbits. The Ang-(1-7) antagonist A779 (8 nmol/1 μL per hour) blocked the improvement in baroreflex gain in CHF. Baroreflex gain increased in CHF+Ang-(1-7) animals when only the vagus was allowed to modulate baroreflex control by acute treatment with the β-1 antagonist metoprolol, indicating increased vagal tone. Baseline renal sympathetic nerve activity was significantly lower, and baroreflex control of renal sympathetic nerve activity was enhanced in CHF rabbits receiving Ang-(1-7). These data suggest that augmentation of central Ang-(1-7) inhibits sympathetic outflow and increases vagal outflow in CHF, thus contributing to enhanced baroreflex gain in this disease state.

Original languageEnglish (US)
Pages (from-to)627-634
Number of pages8
JournalHypertension
Volume58
Issue number4
DOIs
StatePublished - Oct 2011

Keywords

  • angiotensin-(1-7)
  • baroreflex
  • blood pressure
  • heart failure
  • heart rate
  • sympathetic nervous system
  • vagus nerve

ASJC Scopus subject areas

  • Internal Medicine

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