Atherosclerosis and Vascular Injury: The Effect of a Perivascular Nitric Oxide Donor in a Cholesterol-Fed Rabbit Model

Nitric oxide (NO) has been shown to prevent neointimal hyperplasia and decrease atherosclerosis in several animal models. It is a major modulator of vascular homeostasis and has vaso-protective effects against atherosclerosis. However, NO-based therapies with such purposes have not been used in the clinical arena. Our objective was to combine a medical grade elastomer and an NO donor, diethylenetriamine NO adduct (DETA/NO), to determine whether its perivascular administration can attenuate atherosclerosis and vascular injury. Aortic intimal injury was produced using paediatric pulmonary valvoplasty catheter in 22 healthy male New Zealand White rabbits, which were fed a high-cholesterol diet for 4 weeks beforehand. A mixture of the elastomer Silastic and DETA/NO was applied locally to cover the aortas in the experiment group. After 6 additional weeks on the high-cholesterol diet, the aortas and blood samples were harvested for pathologic analysis and comparison with the control group. Mean atherosclerosis and vascular injury surface area was 6.68 x 10(5) mu m(2) in the experiment group, compared with 3.44 x 10(5) mu m(2) in the controls. However, there was no statistically significant difference in atherosclerotic surface area between the two groups. Perivascular application of the NO donor DETA/NO, in the concentration we used, did not prevent atherosclerosis in high cholesterol-fed rabbits. This finding prompts more careful assessment before possible clinical uses.