Am J Hypertens. 2007 Jan;20(1):62-9. Inadequate cytoplasmic antioxidant enzymes response contributes to the oxidative stress in human hypertension. Chaves FJ, Mansego ML, Blesa S, Gonzalez-Albert V, Jimenez J, Tormos MC, Espinosa O, Giner V, Iradi A, Saez G, Redon J. Research Unit, University of Valencia, Valencia, Spain. Untreated hypertensive patients show increased oxidative stress and decreased antioxidant enzyme activity in mononuclear cells. Therefore, the objective of this study was to determine whether or not the low antioxidant enzyme activity observed in mononuclear cells of hypertensive subjects is in part dependent on a defective activity of antioxidant mechanisms. Activity and mRNA level of antioxidant enzymes, CuZn- and Mn-superoxide dismutases, catalase, glutathione peroxidase type 1, and glutathione reductase were simultaneously measured in mononuclear cells of controls (n = 38) and hypertensive subjects (n = 35), in the absence of and during antihypertensive treatment. An increase in oxidative stress and a decrease in the activity of cytoplasmic enzymes were observed in untreated hypertensive patients. Concurrently, CuZn-superoxide dismutase and glutathione reductase mRNA levels were significantly reduced, and glutathione peroxidase type 1 mRNA was slightly reduced. In contrast, increased activity and mRNA levels of the mitochondrial Mn-superoxide dismutase were observed. Antihypertensive treatment, nonpharmacologic with or without a drug regimen of beta-blocker or angiotensin AT1 receptor blocker was administered for a 3-month period. Afterward, after the improvement in oxidative stress during treatment, a recovery of the cytoplasmic antioxidant enzymatic activity and a more profound decrease in mRNA levels were observed for CuZn-superoxide dismutase, glutathione peroxidase type 1, and glutathione reductase. Meanwhile mitochondrial enzymatic activity decreased, as did the mRNA level. The inadequate response of the main cytoplasmatic antioxidant systems, as well as of the enzymes participating in the maintenance of glutathione levels, may contribute to the vulnerability of hypertensives to oxidative stress.