Oxidative stress and vascular dysfunction in ageing: The role of Nox2

S Cahill-Smith, JM Li. University of Surrey, Guildford, UK

Ageing has been recognised to be a major risk factor for the development of cardiovascular disease and growing evidence suggests a role for oxidative stress. Nox2 NADPH oxidase is a major source of reactive oxygen species (ROS) found in the cardiovascular system however, it is unclear of the role of this enzyme in age-related cardiovascular diseases. In this study we used Nox2-deficient (Nox2-/-) mice on a C57BL/6 background and their wild-type controls to investigate the role of Nox2 in age-related vascular dysfunction. Blood pressure, measured by VPR tail-cuff plethysmography and body weight measurements were collected throughout the study. A significant increase was seen in blood pressure in the wild-type mice from young (3-4 month) to ageing (18-20 month) with readings of 126 mmHg and 154 mmHg respectively (P<0.05); however no such increase is seen in the Nox2-/- mice whose blood pressure remains stable with ageing. A significant increase in body weight with ageing is also seen in the wild-type mice in contrast to the Nox2-/- mice which maintain a stable body weight. Groups of mice were culled at young (3-4m), and old (18-24m) age and an organ bath was used to examine the relaxation of aortic rings. There was no significant difference in the maximal vessel relaxation to a nitric oxide donor (sodium nitroprusside) between any of the groups of mice. There was a significant decrease (P<0.05) in the percentage of endothelium-dependent maximal vessel relaxation to acetylcholine in wild-type ageing mice (65%) compared to the young controls (73%). However in the Nox2-/- mice there was an enhanced relaxation to acetylcholine seen in both young (86%) and ageing(82%) (P<0.05) compared to the wild-type mice. The heart weights of all mice were measured and there was no significant difference in the heart/body weight ratio between any of the groups indicating no sign of hypertrophy. The level of superoxide production in aortic sections was measured by DHE fluorescence and a significant decrease in superoxide production is seen in the Nox2-/- mice at both age groups (P<0.05). In conclusion, ageing causes an increase in blood pressure and an increase in endothelial dysfunction and removal of Nox2 reduces blood pressure and improves endothelial dysfunction protecting the vasculature against ageing by reducing the level of ROS in the cardiovascular system.