Blunted reactive hyperaemia and reduced t-PA release in hypertensive and atherosclerotic men

Background: Endothelial dysfunction increases atherothrombotic risk, but the reasons of this association are unclear. An interesting hypothesis postulates a direct relationship between defective endothelial-mediated vasomotion and reduced local release of tissue plasminogen activator (t-PA), the key fibrinolytic control mechanism in man. However, the concept, based upon data obtained by infusing pharmacological concentrations of endothelial-mediated vasodilators, needs testing under more physiological conditions. For this reason, we evaluated t-PA release (REL) during reactive hyperaemia (RH), a physiological local vasodilator response mediated by endothelial-derived compounds produced in response to ischemia. Methods: Forearm blood flow (FBF, strain-gauge plethysmography), arterial (A) and venous (V) t-PA and plasminogen activator inhibitor (PAI)-1 antigen concentrations (ELISA) to derive REL (V-A × FBF), were measured in the right forearm of 7 uncomplicated males (CON, 42±9 yrs, total cholesterol: 190±40 mg/dl) and 6 older (60±8 yrs), hypercholesterolemic (260±15 mg/dl) male patients with atherosclerotic vascular disease (ATH), i.e. a group at high risk for endothelial dysfunction. Data were measured before and 1, 5, 10 minutes after release of a 10-min cuff inflation at the midpoint between systolic and diastolic values. Results: (Means±SD or Medians&Range): Baseline (A) t-PA was higher in ATH than CON (18.6±6.2 vs 9.4±2.4 ng/ml, p