Antioxidants reverse age-related collateral growth impairment

Aging is a major risk factor for the development of cardiovascular diseases, including arterial occlusive disease. Oxidant stress increases with age, and may be a significant factor contributing to vascular dysfunction and disease. We have shown that aging and hypertension impair collateral growth, the natural compensatory response to arterial occlusive disease, and that antioxidants restore collateral growth in young hypertensive rats. The aim of this study was to test the hypothesis that oxidant stress mediates collateral growth impairment in nondiseased, aged rats. Ileal arteries were induced to become collaterals via ligation of adjacent arteries. Growth was assessed at 7 days by repeated in vivo measurements and comparison to same-animal control arteries. Collateral diameter enlargement did not occur in aged rats, but luminal expansion was stimulated by pretreatment with tempol. Co-administration of L-NAME with tempol prevented tempol-mediated collateral development. Expression of p22(phox) mRNA was increased in aged versus young rat arteries, suggesting NAD(P)H oxidase as a source of reactive oxygen species. Treatment with apocynin increased collateral growth capacity, whether administered prior to, or 7 days following, arterial ligation. The results suggest that antioxidant treatment may be useful in promoting collateral growth to compensate for age-related arterial occlusive disease.