Questions:

The NO-sensitive guanylyl cyclase (NO-GC) participates in the regulation of various physiological processes in the vasculature. As the main receptor for nitric oxide (NO), NO-GC is involved in vascular smooth muscle relaxation by increasing cGMP synthesis thereby mediating the regulation of blood pressure. NO synthesis by endothelial NO synthase (eNOS) can be stimulated by the vascular endothelial growth factor (VEGF) which is an important stimulator of angiogenesis. The interconnection between the VEGF and the NO/cGMP pathway is unclear. Moreover, the role of the NO-GC in angiogenesis is still unknown.

Methods:

In order to investigate this issue, a global NO-GC knock-out mouse (GCKO) and an endothelium specific NO-GC knock-out model (EC-GCKO) were generated. These mouse lines were used to determine the role of NO-GC in angiogenesis. In addition, the EC-GCKO line was used to determine the expression and a possible function of NO-GC in the endothelium which is still unknown in the murine system.

Results:

rtPCR was used to prove the presence of NO-GC in the endothelium. To investigate the involvement of the NO/cGMP cascade in VEGF-mediated angiogenesis, the aortic ring assay was employed to compare endothelial sprouting in the different mouse lines. We also used the oxygen-induced retinopathy model (OIR) to monitor vessel loss and regrowth in vivo.

Conclusions:

Our results confirm the presence of NO-GC in murine endothelium and show differences in aortic sprouting and OIR experiments between GCKO and control mice. These data indicate the involvement of NO-GC in the regulation of angiogenesis.