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 language | English |
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Pages (from-to) | 127-35 |
Number of pages | 9 |
Journal | Clinical science |
Volume | 100 |
Issue number | 2 |
Publication status | Published - 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