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.
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Research Article|
December 19 2000
Effects of acute methionine loading and vitamin Con endogenous fibrinolysis, endothelium-dependent vasomotion and platelet aggregation
Catherine LABINJOH
;
Catherine LABINJOH
*Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, U.K.
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David E. NEWBY
;
*Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, U.K.
Correspondence: Dr D. E. Newby, Cardiovascular Research, Department of Cardiology, Royal Infirmary, Edinburgh EH3 9YW, Scotland, U.K. (e-mail d.e.newby@ed.ac.uk).
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Ian B. WILKINSON
;
Ian B. WILKINSON
*Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, U.K.
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Ian L. MEGSON
;
Ian L. MEGSON
*Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, U.K.
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Helen MACCALLUM
;
Helen MACCALLUM
*Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, U.K.
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Vanessa MELVILLE
;
Vanessa MELVILLE
*Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, U.K.
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Nicholas A. BOON
;
Nicholas A. BOON
†Department of Cardiology, Royal Infirmary, Edinburgh EH3 9YW, Scotland, U.K.
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David J. WEBB
David J. WEBB
*Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, U.K.
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Clin Sci (Lond) (2001) 100 (2): 127–135.
Article history
Received:
June 29 2000
Revision Received:
September 12 2000
Accepted:
October 12 2000
Citation
Catherine LABINJOH, David E. NEWBY, Ian B. WILKINSON, Ian L. MEGSON, Helen MACCALLUM, Vanessa MELVILLE, Nicholas A. BOON, David J. WEBB; Effects of acute methionine loading and vitamin Con endogenous fibrinolysis, endothelium-dependent vasomotion and platelet aggregation. Clin Sci (Lond) 1 February 2001; 100 (2): 127–135. doi: https://doi.org/10.1042/cs1000127
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