Maintenance of DNA is an essential part of life sustainment in eukaryotic cells. Apart from being important for homeostasis, and its well-known role in cancer, accumulation of unrepaired DNA damage is a causative factor in organismal ageing. Ageing due to DNA damage is a process of progressive functional loss driven by changes in homeostatic mechanisms that are meant to protect against further accumulation of DNA damage, but that on the other hand result in the problems one encounters during the ageing process. In the past years our lab has shown that these problems include well-known features of vascular dysfunction the are found in aged organisms. With the use of mice that lack key DNA repair enzymes, such as the endonuclease ERCC1, in all body cells, we have shown that defective DNA repair leads to a rapid development of increased blood pressure, decreased organ perfusion, decreased vasodilator responses, increased vascular stiffness, and increased vascular permeability. In animals lacking ERCC1 in endothelial cells or smooth muscle cells we demonstrate that the type of vascular dysfunction depends on the specific cell type in which DNA repair is ablated. Regarding signaling pathways we observed a decreased vasodilator function of the nitric oxide – cGMP axis. This is due to changes in eNOS, phosphodiesterase activity and oxidative stress. As a mediator of dysfunction we found that altered PDE1A and 1C is involved. Current studies with newly developed specific PDE1 inhibitors demonstrate that these drugs can restore vasodilator dysfunction as caused by DNA repair defectiveness, which might have implications for the treatment of vascular ageing.