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AT1 antagonism by eprosartan lowers heart rate variability and baroreflex gain
Authors:Heusser Karsten  Vitkovsky Jan  Schmieder Roland E  Schobel Hans P
Affiliation:Department of Medicine IV/Nephrology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054, Erlangen, Germany. karsten.heusser@gmx.de
Abstract:INTRODUCTION: Blockade of the renin-angiotensin system (RAS) by ACE inhibitors has been demonstrated to reduce total mortality in cardiovascular diseases. This advantage was attributed in part to changes of autonomic cardiovascular control, exemplified by an increase of heart rate variability (HRV) and baroreflex gain (BRG). We sought to assess the effects of the angiotensin type 1 (AT1) receptor blocker eprosartan on HRV and BRG. MATERIALS AND METHODS: In a double-blind randomized cross-over design 25 young males took eprosartan (600 mg/day) and placebo each for a period of 7 days with a wash-out period of at least 4 weeks in between. At the end of the intake phases simultaneous recordings of arterial blood pressure (AP; Finapres) and electrocardiogram (ECG) were taken. Power spectra of HRV and arterial blood pressure variability (APV) were calculated by fast Fourier transform (FFT) and served to calculate BRG. Ang-II levels were measured by radioimmunoassay. RESULTS: Eprosartan tended to lower mean AP, it slightly increased heart rate (HR) (p<0.05), and markedly increased circulating Ang-II levels (p<0.01). Eprosartan diminished the total power of HRV (p<0.05) and the BRG (p<0.01). The low/high frequency (LF/HF) ratio of HRV and the APV were not altered. CONCLUSIONS: AT1 antagonism by eprosartan lowers heart rate variability and baroreflex gain. We speculate that these findings are due to the marked increase in circulating angiotensin II (Ang II). Further studies are needed to clarify whether angiotensin type 1 (AT1) blockers with potential actions inside the blood-brain barrier (BBB) may have different effects on HRV and BRG.
Keywords:Autonomic nervous system  Baroreflex  Heart rate variability  Renin–angiotensin system  ACE  angiotensin-converting enzyme  Ang II  angiotensin II  AP  arterial pressure  APV  arterial pressure variability  ATRAMI  autonomic tone and reflexes after myocardial infarction  AT1  angiotensin II receptor of type 1  AT2  angiotensin II receptor of type 2  BBB  blood–brain barrier  BRG  baroreflex gain  ECG  electrocardiogram  FFT  fast Fourier transform  HF  high frequency (0.15..0.40 Hz)  HR  heart rate  HRV  heart rate variability  LF  low frequency (0.04..0.15 Hz)  MAP  mean arterial pressure  probability of incorrectly rejecting a true null hypothesis  pNN50  percentage of successive normal sinus RR intervals differing >50 ms  RAS  renin–angiotensin system  RMSSD  root mean square of successive normal sinus RR interval differences  S.D.  standard deviation  SDNN  standard deviation of normal sinus RR intervals  S.E.M.  standard error of mean
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