Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Type

Journal article

Journal

Clin sci (lond)

Publication Date

02/2001

Volume

100

Pages

127 - 135

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