Recent clinical and animals studies have shown that collateral growth is impaired in the presence of vascular risk factors, including hypertension. Available evidence suggests that angiotensin converting enzyme inhibitors (ACEI) promote collateral growth in both hypertensive humans and animals; however, the specific mechanisms are not established. This study evaluated the hypothesis that collateral growth impairment in hypertension is mediated by excess superoxide produced by NAD(P)H oxidase in response to stimulation of the angiotensin II (Ang -II) type 1 receptor (AT1R). After ileal artery ligation, mesenteric collateral growth did not occur in untreated young SHR. Significant luminal expansion occurred in collaterals of SHR treated with the superoxide dismutase mimetic tempol, the NAD(P)H oxidase inhibitor apocynin, and the angiotensin converting enzyme inhibitor (ACEI) captopril, but not the Ang -II type 1 and 2 receptor blockers losartan and PD123319. The ACEI enalapril produced equivalent reduction of arterial pressure as captopril but did not promote luminal expansion. This suggests the effects of captopril on collateral growth might result from its anti-oxidant properties. RT-PCR demonstrated that AT1R and angiotensinogen expression was reduced in collaterals of untreated rats. This local suppression of the renin angiotensin system provides a potential explanation for the lack of effect of enalapril and losartan on collateral growth. The results demonstrate the capability of antioxidant therapies, including captopril, to reverse impaired collateral growth and the novel finding that components of the local renin angiotensin system are naturally suppressed in collaterals.