gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Influence of Angiotensin-(1-7)-Receptor Agonist AVE0991 on Heart Rate and Blood Pressure Variability and Baroreceptor Sensitivity

Der Einfluß des Angiotensin-(1-7)-Rezeptor Agonisten AVE0991 auf die Herzfrequenz- und Blutdruckvariabilität sowie Barorezeptorsensitivität

Meeting Abstract (Hypertonie 2004)

  • H. Malberg - Institut für Angwandte Informativ, Forschungszentrum Karlsruhe GmbH
  • N. Wessel - Deutsches Herzzentrum München, Institut für Physik, Universität Potsdam
  • S. Heringer-Walther - Depart. Cardiology, Universitätsmedizin Berlin, Charité, Campus Benjamin Franklin und Dept. Pharmacology, Erasmus Medical Center, Rotterdam, NL
  • H.-P. Schultheiss - Dept. Cardiology, Universitätsmedizin Berlin, Charité, Campus Benjamin Franklin
  • T. Walther - Dept. Cardiology, Universitätsmedizin Berlin, Charité, Campus Benjamin Franklin, Depart. Pharmacology, Erasmus Medical Center (Rotterdam, NL)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP34

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Veröffentlicht: 10. August 2005

© 2005 Malberg et al.
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We have previously shown that the heptapeptide angiotensin (Ang)-(1-7) produces a facilitation of the baroreflex control of heart rate and suggested that endogenous Ang-(1-7) is involved in the improvement of baroreflex sensitivity (BRS) observed in spontaneously hypertensive rats (SHR) during central ACE inhibition. To further investigate the role of the heptapeptide in blood pressure control under physiological conditions in awake animals, the influence of the first non-peptide, orally applicable Ang-(1-7) receptor agonist AVE0991 in SHR was analyzed.

Ten untreated male SHR and 6 age-matched SHR treated by AVE0991 received a telemetry implant (TA11-PA20; DSI, USA) in the carotid artery and were recorded 8 weeks after treatment start. All rats were housed in individual cages in light cycles. The blood pressure signals (500Hz) were monitored for 24h (all 2 hours for 10 min). Heart rate (HRV) and blood pressure variability (BPV) as well as spontaneous BRS was calculated.

AVE0991 significantly decreased HRV (e.g. sdNN, Shannon: wpsum02, wsdvar; all p<10E-03, LF/HF, p<0.01, LF; p<0.05). In BPV, most pronounced changes have been observed for time-domain parameters (e.g. sdNN, Shannon; p<10E-3, meanNN, wpsum02, Wsdvar; p<0.01, polvar6; p<0.05). However, even more significant differences were detected for BRS. While the average slope did not alter, the activation (p<10E-6) and the number of BRS fluctuations by AVE0991 were significantly reduced (p<10E-5). Importantly, all detected differences showed circadian influences, since AVE0991 blunted the rodent-characterizing nightly increase in blood pressure.

Our data demonstrates for the first time that AVE0991 has strong impact on the cardiovascular regulation in SHR and strongly influences the circadian rhythm. This implicates that Ang-(1-7) could be involved in continuous blood pressure control and has, beside earlier demonstrated impact on induced, also profound influence on spontaneous BRS.