PMC:6650341 / 26370-30091 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6650341","sourcedb":"PMC","sourceid":"6650341","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6650341","text":"3.1 Antioxidant effect of antihypertensive drugs\nThe ability of some angiotensin II type 1 receptor blockers305,399 and ACE inhibitors305,400 to reduce ROS production and oxidative stress is well known. The classical renin-angiotensin system increases ROS production22,23,31,34–37,56,57,64 and thus, the beneficial effects of some of the antihypertensive drugs may be due to their ability to inhibit NADPH activity. The sulfhydrylated ACE inhibitors (e.g., captopril, epicaptopril, and S-zofenopril but not enalaprilat, perindoprilat, or quinaprilat401,402) contain a thiol radical that per se has antioxidant properties and may prefer to scavenge general radicals rather than superoxide radicals400,401. Although, the antioxidant effect of sulfhydrylated ACE inhibitors has been ascribed to the thiol group, the vasodilatory effect of S-zofenopril may be due to hydrogen sulfide403. The antioxidant effects of other antihypertensive drugs, such as β adrenoceptor blockers305,404,405 and calcium channel blockers305,406 have been reported, as well. Hypertension and oxidative stress associated with chronic ethanol intake can be prevented by the β-adrenoceptor blocker, nebivolol407. Therefore, part of the beneficial effects of some antihypertensive drugs may due to their ability to decrease ROS production. However, a novel angiotensin II type 1 receptor blocker has been reported to induce oxidative stress in a hepatocellular cell line HepG2408.\nThese disparate effects of anti-hypertensive drugs on ROS production and blood pressure regulation may be related to the fact that, as aforementioned, ROS have beneficial effects on cell function10,13–21. Anti-oxidants at high concentrations may have pro-oxidant effects409 and the excessive antioxidation could have deleterious consequences. For example, a small but continuous production of ROS expression during physical exercise enhances antioxidant defenses and induces the expression of antioxidant enzymes; vitamin C supplementation decreases the endurance capacity in humans and rats410 and diminishes some of the increased skeletal muscle adaptations following acute exercise411. While physiological doses of anti-oxidants may be beneficial, excessive antioxidation could have deleterious consequences because the “remodeling” of skeletal muscles with exercise is dependent on reactive oxygen and nitrogen signaling412. The duration of the antioxidant effects may also be transient. For example, the biomarkers of oxidative DNA damage were attenuated by daily consumption of blueberries for 4 weeks in pre- and stage 1-hypertensive postmenopausal women, however, these effects were not found after 8 weeks413.\nIncreased production of mitochondrial ROS plays a role in the pathogenesis of diabetic nephropathy414 and hypertension355. However, ROS produced by NOX4 can induce endothelial angiogenesis and protect against chronic cardiac overload415. Moreover, diabetic complications are associated with a decrease in mitochondrial ROS production but may help in the preservation of renal glomerular function during hyperglycemia 416,417. Therefore, “normal” physiological levels of mitochondrial superoxide are important for healthy mitochondrial function418.\nThe amount of ROS formed, type of ROS formed, i.e., superoxide versus H2O2, source, duration, and their subcellular locations may be determinants on the consequences of ROS production on cell function. It is universally accepted that a redox imbalance induced by an excessive and uncontrolled ROS production could have deleterious consequences on blood pressure regulation. However, the excessive intake or expression of antioxidants could also have delirious consequences on the cardiovascular 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