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

OBJECTIVES We sought to evaluate whether fasting hyperhomocystinemia reduce s endothelial function by oxidative stress in normotensive, subjects and hy pertensive patients. BACKGROUND Subjects with hyperhomocystinemia have endothelial dysfunction. METHODS In 23 normotensive subjects and 28 hypertensive patients, classifie d into normohomocystinemic and hyperhomocystinemic groups according to homo cysteine plasma levels (<8.7 and > 14.6 mu mol/l, respectively), we studied forearm blood flow changes (strain-gauge plethysmography) induced by intra brachial administration of acetylcholine (0.15 to 15 mug/100 ml tissue per min) or sodium nitroprusside (1 to 4 [mug/100 ml per min), an endothelium; dependent and -independent vasodilator, respectively. Acetylcholine was rep eated with N-G-monomethyl-L-arginine (L-NMMA; 100 mug/100 ml per min), vita min C (8 mg/100 ml per min) and L-NMMA plus vitamin C. RESULTS Normotensive hyperhomocystinemic patients showed a blunted reponse to acetylcholine and a lower inhibiting effiect of L-NMMA on acetylcholine, as compared with normohomocystinemic patients. Although vitamin C was inef fective in normohomocystinemic subjects it. increased the response to acety lcholine and restored the inhibiting effect of L-NMMA on acetylcholine in h yperhomocystinemic patients. Hypertensive hyperhomocystinemic patients show ed a reduced response to acetylcholine, as compared with normohomocystinemi c subjects. In both subgroups, L-NMMA failed to blunt the response to acety lcholine. The potentiating effect of vitamin C on acetylcholine was greater in hyperhomocystinemic patients than in normohomocystinemic subjects, alth ough it restored the inhibitory effect of L-NMMA on acetylcholine-induced v asodilation to the same extent in both groups. Hyperhomocystinemia did not change the response to sodium nitroprusside. CONCLUSIONS In normotensive subjects and hypertensive patients, hyperhomocy stinemia impairs endothelium-dependent vasodilation. It could be related to oxidant activity. (C) 2001 by the American College of Cardiology.