gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

The angiotensin II-receptor antagonist valsartan and the alpha-1-receptor antagonist doxazosin inhibit endothelin-1-induced vasoconstriction in the skin microcirculation in man in vivo

Meeting Abstract (Hypertonie 2004)

  • A. Mitchell - Universitätsklinikum Essen, Klinik für Nieren- und Hochdruckkrankheiten
  • U. Rushentsova - Universitätsklinikum Essen, Klinik für Nieren- und Hochdruckkrankheiten
  • J. Nürnberger - Universitätsklinikum Essen, Klinik für Nieren- und Hochdruckkrankheiten
  • T. Philipp - Universitätsklinikum Essen, Klinik für Nieren- und Hochdruckkrankheiten
  • R. Wenzel - Krankenhaus Zell am See A
  • R. Schäfers - Universitätsklinikum Essen, Klinik für Nieren- und Hochdruckkrankheiten

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP71

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Veröffentlicht: 10. August 2005

© 2005 Mitchell et al.
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Background: Interactions of the sympathetic nervous system (SNS), the renin-angiotensin-system (RAS) and the endothelin-system (ETS) - are being implicated in the pathogenesis of cardiovascular disease. Whereas the interrelationship of SNS and RAS has been well defined, knowledge of their respective interplay with the ETS is limited. We investigated the influence of angiotensin II- (ATII) and alpha-1-receptor-antagonism on endothelin- (ET-1)-induced vasoconstriction.

Study design and methods: 20 healthy male subjects (aged 27±1 years) were included in a double blind, randomised, placebo controlled cross-over study. We used a Laser Doppler imager (moor LDI V 3.0) to evaluate changes in skin blood flow following intradermal injection of ET-1 (10-12 - 10-18 mol) after oral intake of the AT II-receptor antagonist valsartan (80 mg), the alpha-1-receptor antagonist doxazosin (4 mg), or placebo. Responses to AT II (10-12 - 10-18 mol) and noradrenaline (NA, 10-12 - 10-18 mol) were also assessed. Data were analyzed with ANOVA of the dose response curves or t-test and are expressed as arbitrary perfusion units (PU, mean ± SEM).

Results: Following placebo ET-1, AT II- and NA-injections led to a dose dependent vasoconstriction (mean max. constriction: ET-1 -115 ± 78 PU; ATII -84 ± 25 PU; NA -45 ± 35 PU). Valsartan significantly inhibited AT II- but more importantly also ET-1-induced vasoconstriction (ATII: max. +123 ± 55 PU, ET-1 max. +275 ± 144 PU, P= 0.016 and P< 0.001 vs. placebo, respectively). NA-mediated constriction was not influenced by valsartan. Doxazosin inhibited ET-1-induced constriction (max. +322 ± 156 PU, P< 0.001 vs. placebo) but did not influence constriction in response to exogenous NA and AT II.

Conclusion: Both valsartan and doxazosin inhibited ET-1-mediated vasoconstriction in man in vivo, indicating a prominent role for both SNS and RAS in ET-1-mediated vascular responses. Further studies are needed to investigate the underlying mechanisms.