The L-arginine/nitric oxide pathway contributes to the acute release of tissue plasminogen activator in vivo in man.

Abstract:

OBJECTIVE:Effective endogenous fibrinolysis requires rapid release of endothelial tissue plasminogen activator (t-PA). Using the nitric oxide synthase inhibitor, L-NG-monomethylarginine (L-NMMA), we examined the contribution of endogenous nitric oxide to substance P-induced t-PA release in vivo in man. METHODS:Blood flow and plasma fibrinolytic and haemostatic factors were measured in both forearms of 8 healthy male volunteers who received unilateral brachial artery infusions of substance P (2-8 pmol/min) and L-NMMA (1-4 micrograms/min). RESULTS:Substance P caused dose-dependent increases in blood flow (P < 0.001) and plasma t-PA antigen (P = 0.04) and activity (P < 0.001) concentrations confined to the infused forearm, but had no effect on plasminogen activator inhibitor type I (PAI-I) or von Willebrand factor concentrations. In the presence of L-NMMA, substance P again caused significant increases in blood flow (P < 0.001) and t-PA antigen (P = 0.003) and activity (P < 0.001) concentrations but these increases were significantly less than with substance P alone (P < 0.001, P = 0.05 and P < 0.01, respectively). L-NMMA alone significantly reduced blood flow in the infused arm, but had no measurable effect on t-PA or PAI-1 concentrations. CONCLUSIONS:The L-arginine/nitric oxide pathway contributes to substance P-induced t-PA release in vivo in man. This provides an important potential mechanism whereby endothelial dysfunction increases the risk of atherothrombosis through a reduction in the acute fibrinolytic capacity.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Newby DE,Wright RA,Dawson P,Ludlam CA,Boon NA,Fox KA,Webb DJ

doi

10.1016/s0008-6363(98)00017-0

subject

Has Abstract

pub_date

1998-05-01 00:00:00

pages

485-92

issue

2

eissn

0008-6363

issn

1755-3245

pii

S0008-6363(98)00017-0

journal_volume

38

pub_type

临床试验,杂志文章,随机对照试验
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