Skip to main content


We're creating a new version of this page. See preview

  • Poster presentation
  • Open Access

Enhanced vascular cGMP/cGK I signaling and hypotonia in cysteine-rich-protein 2-deficient mice

  • 1Email author,
  • 1,
  • 2,
  • 1,
  • 1,
  • 4,
  • 3,
  • 3,
  • 3,
  • 4,
  • and
  • 1
BMC Pharmacology20055 (Suppl 1) :P48

  • Published:


  • Vascular Smooth Muscle
  • Mean Arterial Pressure
  • Potassium Channel
  • Translation Initiation
  • Vascular Tone

The NO/cGMP signaling pathway plays an important role in vasorelaxation and blood pressure regulation. The predominant effector of cGMP in vascular smooth muscle is cGMP kinase I (cGK I). Established substrates of cGK I in vascular smooth muscle are the large-conductance voltage- and Ca2+-activated (BK) potassium channel, the IP3-receptor-associated cGMP kinase substrate (IRAG) and the myosin phophatase 1 M. Previously, we identified the cysteine-rich protein 2 (CRP2) in blood vessels as a new substrate of cGK I which is specifically phosphorylated by cGK I in vivo. However, the physiological role of CRP2 and its involvement in regulation of vascular tone as an effector of cGMP/cGK I signaling was not known. To elucidate the functional role of CRP2 in vascular smooth muscle, we generated CRP2-deficient (CRP2-/-) mice. The myogenic tone of CRP2-/- tibial small arteries towards stepwise pressure changes revealed no differences when compared to wild type (wt). Unexpectedly, cGMP-mediated relaxation was enhanced in CRP2-/- tibial small arteries and A. saphena. In contrast to cGMP, the cAMP-mediated relaxation was not affected in these vessels. Long-term radiotelemetric recordings revealed a significantly decreased mean arterial pressure (MAP) and an enhanced NO/cGMP signaling in CRP2-/- mice compared to wt. In-depth analysis revealed increased protein levels of cGK I, whereas the expression of cGK I targets such as BK channel and IRAG was not altered in CRP2-/- vessels compared to wt. Interactor screens with CRP2 as a bait revealed a specific interaction with a translation initiation factor. These findings suggest that CRP2 is a specific effector of the vascular NO/cGMP/cGK I signaling in vivo. CRP2 seems to be involved in the regulation of the NO/cGMP/cGK I signaling pathway by modulating cGK I expression. In addition, the CRP2-/- mouse line may serve as an animal model for hypotonia.

Authors’ Affiliations

Pharmakologie und Toxikologie, Pharmazeutisches Institut der Universität Tübingen, Tübingen, 72076, Germany
Institut für Physiologie, Universität Rostock, 18057 Rostock, Germany
Institut für Pharmakologie und Toxikologie, TU München, 80802 München, Germany
Institut für Anatomie, Universität Erlangen, 91054 Erlangen, Germany


© BioMed Central Ltd 2005