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document
Potentiation of bradykinin-induced tissue plasminogen activator release by angiotensin-converting enzyme inhibition . OBJECTIVES The aim of the present study was to determine the effect of angiotensin-converting enzyme ( ACE ) inhibition on the local stimulated release of tissue plasminogen activator ( t-PA ) from the endothelium . BACKGROUND Angiotensin-converting enzyme inhibitor therapy may exert a beneficial effect on the endogenous fibrinolytic balance . METHODS Blood flow and plasma fibrinolytic factors were measured in both forearms of eight healthy males who received unilateral brachial artery infusions of the endothelium-dependent vasodilators substance P ( 2 to 8 pmol/min ) and bradykinin ( 100 to 1,000 pmol/min ) , and the endothelium-independent vasodilator sodium nitroprusside ( 2 to 8 microg/min ) . These measurements were performed on each of three occasions following one week of matched placebo , quinapril 40 mg or losartan 50 mg daily administered in a double-blind randomized crossover design . RESULTS Sodium nitroprusside , substance P and bradykinin produced dose-dependent increases in the blood flow of infused forearm ( analysis of variance [ ANOVA ] , p < 0.001 for all ) . Although sodium nitroprusside did not affect plasma t-PA concentrations , they were increased dose-dependently in the infused forearm by substance P and bradykinin infusion ( ANOVA , p < 0.001 for both ) . Bradykinin-induced release of active t-PA was more than doubled during treatment with quinapril in comparison to placebo or losartan ( two-way ANOVA : p < 0.003 for treatment group , p < 0.001 for t-PA response and p = ns for interaction ) , whereas the substance P response was unaffected . CONCLUSIONS We have shown a selective and marked augmentation of bradykinin-induced t-PA release during ACE inhibition . These findings suggest that the beneficial clinical and vascular effects of ACE inhibition may , in part , be mediated through local augmentation of bradykinin-induced t-PA release .
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Intervention_Physical
Angiotensin-converting enzyme inhibitor therapy
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Intervention_Pharmacological
endothelium-dependent vasodilators substance P
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Intervention_Pharmacological
bradykinin
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Intervention_Pharmacological
endothelium-independent vasodilator sodium nitroprusside
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Intervention_Control
placebo
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Intervention_Pharmacological
quinapril
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Intervention_Pharmacological
losartan
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Intervention_Pharmacological
quinapril
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Intervention_Control
placebo
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Intervention_Pharmacological
losartan
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Outcome_Physical
Blood flow and plasma fibrinolytic factors
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Outcome_Physical
increases in the blood flow
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Outcome_Physical
plasma t-PA concentrations
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Outcome_Physical
release of active t-PA
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Outcome_Physical
substance P response was unaffected