Chronic endothelin-1 blockade reduces sympathetic nerve activity in rabbits with heart failure

J. L. Liu, R. U. Pliquett, E. Brewer, K. G. Cornish, Y. T. Shen, I. H. Zucker

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44 Scopus citations

Abstract

Endothelin-1 (ET-1) is elevated in chronic heart failure (CHF). In this study, we determined the effects of chronic ET-1 blockade on renal sympathetic nerve activity (RSNA) in conscious rabbits with pacing-induced CHF. Rabbits were chronically paced at 320-340 beats/min for 3-4 wk until clinical and hemodynamic signs of CHF were present. Resting RSNA and arterial baroreflex control of RSNA were determined. Responses were determined before and after the ET-1 antagonist L-754, 142 (a combined ETA and ETB receptor antagonist, n = 5) was administered by osmotic minipump infusion (0.5 mg·kg-1·h-1 for 48 h). In addition, five rabbits with CHF were treated with the specific ETA receptor antagonist BQ-123. Baseline RSNA (expressed as a percentage of the maximum nerve activity during sodium nitroprusside infusion) was significantly higher (58.3 ± 4.9 vs. 27.0 ± 1.0, P < 0.001), whereas baroreflex sensitivity was significantly lower in rabbits with CHF compared with control (3.09 ± 0.19 vs. 6.04 ± 0.73, P < 0.001). L-754, 142 caused a time-dependent reduction in arterial pressure and RSNA in rabbits with CHF. In addition, BQ-123 caused a reduction in resting RSNA. For both compounds, RSNA returned to near control levels 24 h after removal of the minipump. These data suggest that ET-1 contributes to sympathoexcitation in the CHF state. Enhancement of arterial baroreflex sensitivity may further contribute to sympathoinhibition after ET-1 blockade in heart failure.

Original languageEnglish (US)
Pages (from-to)R1906-R1913
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume280
Issue number6 49-6
DOIs
StatePublished - 2001

Keywords

  • Autonomic nervous system
  • Baroreflex
  • ET receptors
  • Myocardial dysfunction
  • Neurohormones

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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