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CLINICAL RESEARCH: PHARMACOLOGY

Acute aldosterone antagonism improves cardiac vagal control in humans

Janine Fletcher, BSc (Hons) PhD^*, Ashesh N. Buch, MBChB, MRCP^,*, Helen C. Routledge, BSc, MBChB, MRCP, Saqib Chowdhary, MBBS PhD, MRCP, John H. Coote, PhD, DSc^* and Jonathan N. Townend, MBChB, MD, FRCP

^* Department of Physiology, University of Birmingham, Edgbaston, Birmingham, United Kingdom
Department of Cardiovascular Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom

Manuscript received June 24, 2003; revised manuscript received October 7, 2003, accepted October 13, 2003.

^* Reprint requests and correspondence: Dr. Ashesh N. Buch, Research Fellow in Cardiology, Department of Cardiovascular Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom.
asheshbuch{at}hotmail.com

OBJECTIVES: We have examined the acute effects (<45 min) of aldosterone antagonism on heart rate variability and baroreflex sensitivity, markers of cardiac vagal control, in 13 healthy subjects.

BACKGROUND: Evidence for the beneficial effects of aldosterone antagonists comes from studies showing increased survival rates following their addition to standard heart failure therapy. Many mechanisms have been suggested for this action, including effects upon the autonomic nervous system.

METHODS: Heart rate variability and baroreflex sensitivity were examined 30 min following the administration of potassium canrenoate (intravenous) (aldosterone antagonist) or saline (control).

RESULTS: Active treatment reduced resting heart rate (–6 ± 1 beats/min [mean ± standard error mean]) compared to control (0 ± 1 beat/min) (p < 0.001) and increased measures of high frequency (HF) heart rate variability. Root mean square of successive RR interval differences increased by 21 ± 5 ms versus –6 ± 5 ms control (p < 0.001); HF power increased by 1,369 ± 674 ms²with aldosterone antagonism compared to –255 ± 431 ms² following saline infusion (p < 0.01). Baroreflex sensitivity (alpha-HF) was increased after active treatment (+4 ± 2 ms/mm Hg vs. 0 ± 1 ms/mm Hg control [p < 0.05]). No changes in plasma potassium levels were observed.

CONCLUSIONS: These results provide evidence that aldosterone antagonists acutely improve cardiac vagal control, irrespective of any diuretic effects, and may in part explain their beneficial effects in treatment of heart failure.

Abbreviations and Acronyms   HF = high frequency   LF = low frequency   MR = mineralocorticoid receptors   NO = nitric oxide   pNN50 = percentage of successive RR interval differences exceeding 50 ms   RMSSD = root mean square of successive RR interval differences   SDNN = standard deviation of RR interval values

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