Deoxycorticosterone acetate (DOCA)-salt hypertension has an important endothelin-1 (ET-1)-dependent component. ET-1-induced vascular damage may be mediated in part by oxidative stress and vascular inflammation. Homozygous osteopetrotic mice (Op/Op), deficient in macrophage colony-stimulating factor (m-CSF), exhibit reduced inflammation. We investigated in osteopetrotic mice (Op/Op) the effects of DOCA-salt hypertension, on vascular structure, function and oxidative stress, the latter as manifested by reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase activity. Mice were implanted with DOCA (200 mg/mouse, under 5% isofluorane anesthesia) and given saline for 14 days. Systolic blood pressure (mmHg) was significantly increased (146±2 and 138±1, P<0.001 vs. basal 115±3 and 115±3, respectively) by DOCA-salt in wild type (+/+) and heterozygous mice (Op/+), but not in Op/Op (130±1 vs. basal 125±3). Norepinephrine contractile response was significantly enhanced while acetylcholine endothelium-dependent vasodilation were significantly impaired in DOCA-salt-treated +/+ and Op/+ compared to controls. No changes in norepinephrine-induced contraction and acetylcholine-induced relaxation were observed in DOCA-salt Op/Op. DOCA-salt +/+ and Op/+ mice had significantly increased mesenteric resistance artery media-to-lumen ratio and media cross-sectional area, neither of which were altered in Op/Op mice. Basal vascular superoxide production and NAD(P)H oxidase activity, vascular cell adhesion molecule (VCAM)-1 expression and macrophage infiltration were significantly increased only in DOCA-salt +/+. Thus, m-CSF-deficient mice developed less endothelial dysfunction, vascular remodeling and oxidative stress induced by DOCA-salt than +/+ and Op/+, suggesting that inflammation may play a role in DOCA-salt hypertension, a model that results in part from effects of endothelin-1 which has pro-inflammatory actions.