Abstract 118: Nebivolol Therapy Enhances Endothelial Fibrinolytic Capacity in Adults with Elevated Blood Pressure
Impaired endothelial fibrinolytic function contributes to increased thrombotic risk with elevated blood pressure . In vitro data suggests that the antihypertensive, nebivolol (N), favorably effects the fibrinolytic system, but there is no in vivo clinical evidence that N treatment improves endothelial fibrinolytic function. We hypothesized that chronic N therapy will increase the capacity of the endothelium to release tissue-type plasminogen activator (t-PA) in adults with elevated blood pressure (BP ≥ 130/85 mm Hg). In an ongoing study, 36 middle-aged adults (age: 44-67 years) were treated for 12 weeks: 12 with N (5 mg/d; BP 141/86±2/2 mmHg); 12 with metoprolol succinate (M: 100 mg/d; 140/90±3/2 mmHg); and 12 with placebo (P; 138/85±2/2 mmHg). Before and after intervention, net endothelial release of t-PA was determined, in vivo , in response to intrabrachial infusions of bradykinin (BK: 125-500 ng/min) and sodium nitroprusside (SNP: 2-8 μg/min). Subject characteristics (age, BMI, systolic and diastolic BP) were similar between the groups. Blood pressure was lowered (P< 0.05) to a similar extent by both N (124/78±3/2 mmHg) and M (124/78±3/1 mmHg) but unchanged by P (134/80±3/2 mmHg). Endothelial t-PA release in response to BK was not significantly different between the N (-2.8±1.4 to 49.2±5.6 ng/100 mL tissue/min), M (-0.5±1.3 to 53.5±8.5 ng/100 mL tissue/min) and P (0.1±1.1 to 52.0±5.6 ng/100 mL tissue/min) groups prior to intervention. After intervention, only N therapy affected t-PA release; the capacity of the endothelium to release t-PA in the N group was significantly higher (-1.9±1.6 to 72.6±7.1 ng/100 mL tissue/min; P< 0.05). Total amount of t-PA released (area under the BK curve) markedly increased (45%) in response to N (308±39 vs 445±47 ng/100 mL tissue; P< 0.05). In contrast, endothelial t-PA release was not significantly altered by M (-1.6±1.1 to 54.0±6.1 ng/100 mL tisuue/min). As expected, t-PA release was unchanged with P. These results demonstrate that, in spite of similar reductions in blood pressure, N, but not M, treatment increases the capacity of the endothelium to release t-PA in adults with elevated blood pressure. Enhanced endothelial fibrinolytic function with N may provide an important vascular benefit in this at risk population.