ARE FREE-RADICALS INVOLVED IN THE PATHOBIOLOGY OF HUMAN ESSENTIAL-HYPERTENSION

Possible involvement of reactive oxygen species and nitric oxide in th e pathogenesis of human essential hypertension was investigated. It wa s observed that both superoxide anion and hydrogen peroxide production by polymorphonuclear leukocytes and the plasma levels of lipid peroxi des are higher in uncontrolled essential hypertension compared with no rmal controls. Nitric oxide levels measured as its stable metabolite n itrite, 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 afte r the control of hypertension by drugs. The concentrations of anti-oxi dants such as vitamin E and superoxide dismutase were found to be decr eased in patients with uncontrolled hypertension. Several anti-hyperte nsive drugs inhibited lipid peroxidation in vitro. Angiotensin-II, a p otent vasoconstrictor, stimulated free radical generation in normal le ukocytes which could be blocked by calmodulin antagonists. These resul ts suggest that an increase in free radical generation and a simultane ous decrease in the production of nitric oxide and anti-oxidants such as SOD and vitamin E occurs in essential hypertension. This increase i n free radical generation can inactivate prostacyclin and nitric oxide and decrease their half life which can lead to an increase in periphe ral vascular resistance and hypertension.