Effects of acute methionine loading and vitamin C on endogenous fibrinolysis, endothelium-dependent vasomotion and platelet aggregation

C Labinjoh, D E Newby, I B Wilkinson, I L Megson, H MacCallum, V Melville, N A Boon, D J Webb

Research output: Contribution to journalArticlepeer-review

Abstract

We assessed forearm blood flow and plasma fibrinolytic factors in eight healthy males who received unilateral brachial artery infusions of the endothelium-dependent vasodilator, substance P, and the endothelium-independent vasodilator, sodium nitroprusside. These measurements, together with platelet aggregation studies, were performed on four occasions after double-blind randomized ingestion of placebo, methionine (0.1 mg/kg), vitamin C (2 g) and methionine plus vitamin C. Blood flow and platelet aggregation responses were unaffected by methionine loading. Substance P caused dose-dependent increases in plasma tissue plasminogen activator (t-PA) antigen (from 3.0+/-0.1 to 4.7+/-0.4 ng/ml; P<0.001) and activity (from 1.2+/-0.2 to 4.2+/-0.4 i.u./ml; P<0.001), which were augmented during acute methionine loading (4.7+/-0.4 to 5.6+/-0.5 ng/ml and 4.2+/-0.4 to 5.5+/-0.9 i.u./ml respectively; P</=0.05). Moreover, the estimated net release of t-PA was enhanced during methionine loading (two-way ANOVA; P=0.02), but this was unaffected by vitamin C supplementation. We conclude that, in the absence of alterations in endothelium-dependent vasomotion or platelet aggregation, substance P-induced t-PA release is enhanced following methionine loading. This suggests that the acute endogenous fibrinolytic capacity is augmented during acute hyperhomocysteinaemia in healthy humans via an oxidation-independent mechanism.

Original languageEnglish
Pages (from-to)127-35
Number of pages9
JournalClinical science
Volume100
Issue number2
Publication statusPublished - Feb 2001

Keywords

  • Acute Disease
  • Adult
  • Ascorbic Acid
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endothelium, Vascular
  • Fibrinolysis
  • Forearm
  • Humans
  • Hyperhomocysteinemia
  • Male
  • Methionine
  • Nitroprusside
  • Platelet Aggregation
  • Regional Blood Flow
  • Substance P
  • Tissue Plasminogen Activator
  • Vasodilation
  • Vasodilator Agents

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