Mechanisms responsible for endothelial dysfunction induced by fasting hyperhomocystinemia in normotensive subjects and patients with essential hypertension

Abstract OBJECTIVES We sought to evaluate whether fasting hyperhomocystinemia reduces endothelial function by oxidative stress in normotensive subjects and hypertensive patients. BACKGROUND Subjects with hyperhomocystinemia have endothelial dysfunction. METHODS In 23 normotensive subjects and 28 hypertensive patients, classified into normohomocystinemic and hyperhomocystinemic groups according to homocysteine plasma levels ( 14.6 μmol/l, respectively), we studied forearm blood flow changes (strain-gauge plethysmography) induced by intrabrachial administration of acetylcholine (0.15 to 15 μg/100 ml tissue per min) or sodium nitroprusside (1 to 4 μg/100 ml per min), an endothelium-dependent and -independent vasodilator, respectively. Acetylcholine was repeated with N G -monomethyl- L -arginine ( L -NMMA; 100 μg/100 ml per min), vitamin C (8 mg/100 ml per min) and L -NMMA plus vitamin C. RESULTS Normotensive hyperhomocystinemic patients showed a blunted response to acetylcholine and a lower inhibiting effect of L -NMMA on acetylcholine, as compared with normohomocystinemic patients. Although vitamin C was ineffective in normohomocystinemic subjects, it increased the response to acetylcholine and restored the inhibiting effect of L -NMMA on acetylcholine in hyperhomocystinemic patients. Hypertensive hyperhomocystinemic patients showed a reduced response to acetylcholine, as compared with normohomocystinemic subjects. In both subgroups, L -NMMA failed to blunt the response to acetylcholine. The potentiating effect of vitamin C on acetylcholine was greater in hyperhomocystinemic patients than in normohomocystinemic subjects, although it restored the inhibitory effect of L -NMMA on acetylcholine-induced vasodilation to the same extent in both groups. Hyperhomocystinemia did not change the response to sodium nitroprusside. CONCLUSIONS In normotensive subjects and hypertensive patients, hyperhomocystinemia impairs endothelium-dependent vasodilation. It could be related to oxidant activity.