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

J Am Coll Cardiol. 2001 Oct;38(4):1106-15. doi: 10.1016/s0735-1097(01)01492-9.


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 micromol/l, respectively), we studied forearm blood flow changes (strain-gauge plethysmography) induced by intrabrachial administration of acetylcholine (0.15 to 15 microg/100 ml tissue per min) or sodium nitroprusside (1 to 4 microg/100 ml per min), an endothelium-dependent and -independent vasodilator, respectively. Acetylcholine was repeated with N(G)-monomethyl-L-arginine (L-NMMA; 100 microg/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.

MeSH terms

  • Acetylcholine / pharmacology
  • Adult
  • Endothelium, Vascular / physiopathology*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Forearm / blood supply
  • Humans
  • Hyperhomocysteinemia / physiopathology*
  • Hypertension / physiopathology*
  • Male
  • Microcirculation
  • Middle Aged
  • Oxidative Stress*
  • Regional Blood Flow
  • Vasodilator Agents / pharmacology
  • omega-N-Methylarginine / pharmacology


  • Enzyme Inhibitors
  • Vasodilator Agents
  • omega-N-Methylarginine
  • Acetylcholine