gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

Rho-kinase contributes to basal vascular tone in man: role of endothelium-derived nitric oxide

Die Rho-kinase reguliert den basalen Tonus der Widerstandsgefäße: Rolle von endothelialem Stickstoffmonoxid

Meeting Abstract

  • E. Büssemaker - Universitätsklinikum Carl Gustav Carus, Dresden (Dresden, D)
  • F. Pistrosch - Universitätsklinikum Carl Gustav Carus, Dresden (Dresden, D)
  • P. Gross - Universitätsklinikum Carl Gustav Carus, Dresden (Dresden, D)
  • J. Passauer - Universitätsklinikum Carl Gustav Carus, Dresden (Dresden, D)
  • R.P. Brandes - J.-W.-Goethe Universität Frankfurt (Frankfurt, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP150

The electronic version of this article is the complete one and can be found online at:

Published: August 8, 2006

© 2006 Büssemaker et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Phosphorylation of the myosin light chain (MLC) determines the calcium sensitivity of the contractile apparatus and therefore has an important role for vascular smooth muscle contraction. MLC phosphorylation is dependent on the activity of the MLC kinase and the MLC phosphatase (MLCPh). The latter enzyme is inhibited through phosphorylation by the rho-associated kinase (ROK). An increased activity of ROK has been reported in animal models of hypertension. Besides its effect on vascular smooth muscle cells ROK has been also suggested to inhibit endothelial nitric-oxide(edNO) generation. The role of ROK for the regulation of vascular tone in humans has not been fully established. We studied the effect of the selective ROK inhibitor fasudil on foreram blood flow (FBF) in 10 healthy volunteers by venous-occlusion plethysmography. To unmask the role of edNO fasudil was infused after pretreatment with the NO-synthase (NOS) inhibitor l-NMMA (16 µmol/min). In control experiments FBF was reduced to a similar degree by infusion of noradrenaline before fasudil. Moreover, the effect of fasudil on the constrictor response to endothelin-1 (ET) was recorded. Infusion of fasudil markedly increased FBF in a dose-dependent manner (139%±16, 175%±21, 219%±31, 300%±31 at 10, 20, 40, 80 µg/min; ratio between infused and non-infused arm with baseline=100%). No systemic effects were observed. Fasudil abolished the vasoconstrictor effect to the ROK agonist ET (5 pmol/min). The fasudil(80 µmol/min)-induced time-dependent (10, 20, 30, 40 min) increase in FBF was significantly blunted by l-NMMA but not by noradrenaline (164%±36, 189%±36, 202%±44, 220%±36 vs 231%±19, 294%±18, 299%±17, 318%±19). Contributing to the understanding of the role of ROK for vascular homeostasis in man our results show that: 1) Basal vascular tone in healthy volunteers is dependent on ROK. 2) The constrictor response to endothelin-1 involves activation of ROK. 3) ROK causes vasoconstriction at least partly by inhibiting the generation of edNO. Hence ROK inhibition could prove beneficial in situations with increased ET- and decreased NO-mediated tone such as arterial hypertension.