Are Free Radicals Involved in the Pathobiology of Human Essential Hypertension?

Abstract

Possible involvement of reactive oxygen species and nitric oxide in the pathogenesis of human essential hypertension was investigated. It was observed that both superoxide anion and hydrogen peroxide production by polymorphonuclear leukocytes and the plasma levels of lipid peroxides are higher in uncontrolled essential hypertension compared with normal controls. Nitric oxide levels measured as its stable metabolite nitrite, as an index of nitric oxide synthesis, revealed its levels to be low in hypertensive patients. Superoxide anion, hydrogen peroxide, lipid peroxides and nitric oxide levels reverted to normal values after the control of hypertension by drugs. The concentrations of anti-oxidants such as vitamin E and superoxide dismutase were found to be decreased in patients with uncontrolled hypertension. Several anti-hypertensive drugs inhibited lipid peroxidation in vitro. Angiotensin-II, a potent vasoconstrictor, stimulated free radical generation in normal leukocytes which could be blocked by calmodulin antagonists. These results suggest that an increase in free radical generation and a simultaneous decrease in the production of nitric oxide and anti-oxidants such as SOD and vitamin E occurs in essential hypertension. This increase in free radical generation can inactivate prostacyclin and nitric oxide and decrease their half life which can lead to an increase in peripheral vascular resistance and hypertension.

Evaluation of the antioxidant response in the plasma of healthy or hypertensive subjects after short-term exercise

“…Several lines of evidence suggest that hypertension is associated with enhanced oxidative stress. 9,[31][32][33] In particular, it has been proposed that superoxide anions might trigger the development of hypertension, by inactivating endothelium-derived nitric oxide, thus impairing its beneficial and protective effects on the vessel wall. 9 In essential hypertension, both the plasma levels of lipid peroxides and the leucocyte production of superoxide anion or hydrogen peroxide were found increased, 32 while the levels of antioxidants, including Toc, were found decreased.…”

“…9,[31][32][33] In particular, it has been proposed that superoxide anions might trigger the development of hypertension, by inactivating endothelium-derived nitric oxide, thus impairing its beneficial and protective effects on the vessel wall. 9 In essential hypertension, both the plasma levels of lipid peroxides and the leucocyte production of superoxide anion or hydrogen peroxide were found increased, 32 while the levels of antioxidants, including Toc, were found decreased. 31,32 A body of information on the improvement of endotheliumdependent vasodilation by antioxidants is available, and confirms that increased ROS production plays a major role in the pathogenesis of hypertension.…”

“…9 In essential hypertension, both the plasma levels of lipid peroxides and the leucocyte production of superoxide anion or hydrogen peroxide were found increased, 32 while the levels of antioxidants, including Toc, were found decreased. 31,32 A body of information on the improvement of endotheliumdependent vasodilation by antioxidants is available, and confirms that increased ROS production plays a major role in the pathogenesis of hypertension.…”

“…As a matter of fact, recent evidence suggests that hypertensive patients exhibit in plasma a significantly higher production of this free radical than control subjects. 31,32 Excess endothelial superoxide generation has been in turn suggested to be one of the factors causing hypertension. 5 The decreased NO-dependent vasodilator function in hypertension was mostly related to oxidative stress brought about by superoxide radicals.…”

Assessment of Oxidative Stress Markers and Carotid Artery Intima-Media Thickness in Elderly Patients Without and with Coronary Artery Disease

“…ROS and oxLDL may play a critical role in the pathophysiology of hypertension. The involvement of reactive oxygen intermediates in essential hypertension is also suggested by the increased level of lipid peroxides and decreased concentrations of antioxidant vitamin E in plasma of essential hypertensive patients [10].…”