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 hea lthy males who received unilateral brachial artery infusions of the endothe lium-dependent vasodilator, substance P. and the endothelium-independent va sodilator, sodium nitroprusside. These measurements. together with platelet aggregation studies, were performed on four occasions after double-blind r andomized ingestion of placebo, methionine (0.1 mg/kg). vitamin C (2 g) and methionine plus vitamin C. Blood flow and platelet aggregation responses w ere unaffected by methionine loading. Substance P caused dose-dependent inc reases 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 loadi ng (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 less than or equal to 0.05). Moreover, the estimated net r elease of t-PA was enhanced during methionine loading (two-way ANOVA; P = 0 .02), but this was unaffected by vitamin C supplementation. We conclude tha t. in the absence of alterations in endothelium-dependent vasomotion or pla telet aggregation, substance P-induced t-PA release is enhanced following m ethionine loading. This suggests that the acute endogenous fibrinolytic cap acity is augmented during acute hyperhomocysteinaemia in healthy humans via an oxidation-independent mechanism.