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CLINICAL STUDY

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

^a Department of Internal Medicine, University of Pisa, Pisa, Italy

Manuscript received August 23, 2000; revised manuscript received June 1, 2001, accepted June 20, 2001.

Reprint requests and correspondence: Dr. Agostino Virdis, Department of Internal Medicine, University of Pisa, Via Roma, 56100 Pisa, Italy
avirdis{at}med.unipi.it

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 (<8.7 and >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.

Abbreviations and Acronyms   BP = blood pressure   FBF = forearm blood flow   H-HCY = hyperhomocystinemia   L-NMMA = NG-monomethyl-L-arginine   NO = nitric oxide   SNP = sodium nitroprusside

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