Effects of acute methionine loading and vitamin C on endogenous fibrinolysis, endothelium-dependent vasomotion and platelet aggregation.
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.
Labinjoh
C
C
Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, U.K.
Newby
D E
DE
Wilkinson
I B
IB
Megson
I L
IL
MacCallum
H
H
Melville
V
V
Boon
N A
NA
Webb
D J
DJ
D000208:Acute Disease; D000328:Adult; D001205:Ascorbic Acid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D005542:Forearm / Q000098:blood supply; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008715:Methionine; D009599:Nitroprusside / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000097:blood; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; D013373:Substance P; D008715:Methionine; D010959:Tissue Plasminogen Activator; D001205:Ascorbic Acid