gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Hemodynamic and Humoral Effects of the ET-A-selective Endothelin Antagonist Darusentan in Young, Healthy Men

Hämodynamische und humorale Effekte des ET-A-selektiven Endothelin-Antagonisten Darusentan bei jungen, gesunden Probanden

Meeting Abstract (Hypertonie 2003)

  • presenting/speaker A. Mitchell - Universitätsklinikum Essen, ABBOTT Deutschland (Essen, Ludwigshafen, D)
  • S. Bührmann - Universitätsklinikum Essen, ABBOTT Deutschland (Essen, Ludwigshafen, D)
  • K. Rübsamen - Universitätsklinikum Essen, ABBOTT Deutschland (Essen, Ludwigshafen, D)
  • C. Jürgens - Universitätsklinikum Essen, ABBOTT Deutschland (Essen, Ludwigshafen, D)
  • J. Nürnberger - Universitätsklinikum Essen, ABBOTT Deutschland (Essen, Ludwigshafen, D)
  • R.F. Schäfers - Universitätsklinikum Essen, ABBOTT Deutschland (Essen, Ludwigshafen, D)
  • T. Philipp - Universitätsklinikum Essen, ABBOTT Deutschland (Essen, Ludwigshafen, D)
  • R.R. Wenzel - Universitätsklinikum Essen, ABBOTT Deutschland (Essen, Ludwigshafen, D)

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochP24

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2003/03hoch124.shtml

Veröffentlicht: 11. November 2004

© 2004 Mitchell et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Background

Endothelin 1 (ET) is the strongest endogenous vasoconstrictor in humans and mediates its effects via ETA and ETB receptors. Endothelin antagonists are being developed as a new class of antihypertensives. In this study we investigated the systemic hemodynamic and humoral effects of the ETA selective antagonist Darusentan in young, healthy males.

Study design and methods

22 healthy male subjects (aged 27.4 ± 1 years) were included in a double blind, randomised, placebo controlled cross-over study. On two study days (at least one week apart) blood pressure (BP) and heart rate (HR) were determined after 30 minutes at rest (baseline) and after 2, 4 and 24 hours following oral ingestion of 100 mg Darusentan or placebo respectively. In 8 subjects total peripheral resistance (TPR) was measured at baseline and 2 hours after drug ingestion. A handgrip test was performed after 2.5 h to stimulate the SNS. At 0, 2, 2.5, 6 and 24 hours blood samples were collected for determination of noradrenaline (NA), angiotensin II (Ang II), ET plasma concentrations and plasma drug concentrations. Statistical significance was assessed by ANOVA (dose response curve) and t-test. Data are shown as mean changes vs. baseline ± SEM.

Results

Darusentan significantly reduced systolic BP (-5.7 ± 1.7 mmHg at 4 hours, p< 0.01). Diastolic BP and heart rate remained essentially unchanged. TPR was reduced after application of Darusentan (Darusentan: -132.4 ± 104.5 dyne x sec x cm-5, placebo: 64.4 ± 60.4 dyne x sec x cm-5, p= 0.06). Plasma NA and ET concentrations rose significantly following administration of Darusentan (p= 0.025 and p< 0.0001), the rise in Ang II was borderline significant (p= 0.06).

Conclusion

100 mg oral Darusentan acutely reduced systolic BP and TPR with reflectory activation of the SNS in young, healthy males. Future studies will have to determine the effects of a chronic administration of Darusentan on patients with hypertension and/or cardiovascular disease.