P-469: Downregulation of cytoplasmic antioxidant enzymes contributes to the oxidative stress in human hypertension

• Published in: American journal of hypertension Vol. 18; no. S4; p. 177A
• Main Authors: Chaves, Felipe J., Mansego, Maria L., Blesa, Sebastian, Gonzalez-Albert, Veronica, Jimenez, Jorge, Tormos, Maria C., Espinosa, Olga, Giner, Vicente, Saez, Guillermo, Redon, Josep
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2005
• Subjects: Antioxidant Enzymes; Mechanisms; Oxidative Stress
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/j.amjhyper.2005.03.486

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. Subjects and Methods: Activity and mRNA level of antioxidant enzymes (RT-quantitative PCR), CuZn- and Mn-superoxide dismutases, catalase, glutathione peroxidase type 1 and glutathion reductase were simultaneously measured in mononuclear cells of controls (n=12) and hypertensive subjects (42), in absence of and during 3 months of antihypertensive treatment, non-pharmacological with or without a drug regimen of beta-blocker or angiotensin AT1-receptor blocker. Results: 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 glutathion 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. During the antihypertensive treatment, following 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 glutathion reductase. Meanwhile, mitochondrial enzymatic activity decreased as did the level of mRNA. Conclusions: A downregulation phenomenon of cytoplasmic antioxidant enzymes and in enzymes participating in the maintenance of glutathione levels was found in mononuclear cells of subjects with essential hypertension. This downregulation may contribute to the vulnerability of hypertensives to oxidative stress.