The nitric oxide (NO) receptor guanylyl cyclase (NO-GC) is expressed in the vasculature in several different cell types. Endothelial NO mediates its effects mostly by stimulating NO-GC and thereby increasing cGMP synthesis.

Increased NO and cGMP production has been reported in rat, porcine or bovine aorta and human umbilical vein cells upon exposure to vascular endothelial growth factor (VEGF), a key factor for angiogenesis. However, for the murine system, information on the role of NO-GC in endothelial cells is still obscure.

Primary microvascular lung endothelial cells of wild type mice did not lead to a detectable cGMP production after treatment with NO. The attempt to localize NO-GC in the endothelium of various types of blood vessels by immunofluorescence using a specific antibody against the enzyme was unsuccessful. These data indicate that NO-GC is not expressed in mouse endothelial cells.

In order to avoid artefacts from cell culture we generated endothelial-specific NO-GC knock-out mice (EC-GCKO) using the Tie2-Cre line. First characterisation showed no difference in vasorelaxation and systolic blood pressure between EC-GCKO and wild type animals.

The putative participation of endothelial NO-GC in vessel development was investigated by measuring the growth of retinal vessels at postnatal day 7. There was no difference in vessel development between WT and EC-GCKO animals but a significant reduction in global GCKO mice. Using the oxygen-induced retinopathy model, which allows monitoring vessel loss, vessel regrowth and pathological angiogenesis, we will be able to show whether NO-generated cGMP in endothelial cells participates in these processes.