Effect of Copper-Zinc Superoxide Dismutase on Endothelium-Dependent Vasodilation in Patients With Essential Hypertension

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Abstract
Patients with essential hypertension have abnormal endothelium-dependent vasodilation related to decreased nitric oxide activity. The specific mechanism responsible for this abnormality is unknown. Recent studies in hypertensive animals have suggested an augmented destruction of nitric oxide by superoxide anions. Therefore, in the present study we aimed to investigate whether this mechanism is responsible for the abnormal vasodilator function of hypertensive patients. To this end, we studied the vascular responses to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct smooth muscle dilator) before and after combined administration of copper-zinc superoxide dismutase (a scavenger of superoxide anions with poor intracellular penetrance; 6000 U/min) in 20 healthy control subjects (11 men and 9 women; aged 50±6 years) and 20 hypertensive patients (13 men and 7 women; aged 51±9 years). Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by plethysmography. The vasodilator response to acetylcholine was significantly blunted in hypertensive patients compared with control subjects (maximal flow: 8.2±4 versus 12.7±3 mL/min per 100 mL; P <.02); however, no difference was observed in the response to sodium nitroprusside (8.1±4 versus 9.5±3 mL/min per 100 mL). In healthy control subjects superoxide dismutase infusion did not modify the vasodilator response to acetylcholine (maximal flow: 12.7±3 before versus 12.1±3 after superoxide dismutase). Similarly, in hypertensive patients superoxide dismutase infusion did not alter the response to acetylcholine (maximal flow: 8.2±4 versus 7.7±4). Prolonged (up to 60 minutes) infusion of higher doses (24 000 U/min) of copper-zinc superoxide dismustase did not modify the response to acetylcholine in either healthy control subjects or hypertensive patients. The administration of this form of superoxide dismutase did not modify the response to sodium nitroprusside in either group. These findings confirm previous observations of impaired endothelium-dependent vasodilation in patients with essential hypertension and demonstrate that copper-zinc superoxide dismutase does not alter these responses.