Abstract 15536: Chronic Nebivolol Treatment Suppresses Endothelin-1-Mediated Vasoconstrictor Tone in Adults with Elevated Blood Pressure
Introduction: Endothelin (ET)-1 plays a major role in the pathophysiology of clinical hypertension and contributes to the elevated cardiovascular risk in this population. In vitro data suggests that the antihypertensive, nebivolol (N), suppresses vascular ET-1 production; however, there is no in vivo clinical evidence that N reduces ET-1-mediated vasoconstrictor tone.
Hypothesis: We hypothesized that chronic N therapy will reduce ET-1-mediated vasoconstrictor tone in adults with elevated blood pressure (BP ≤ 130/85 mm Hg).
Methods: In an ongoing study, 30 middle-aged adults were treated for 12 weeks: 10 with N (5 mg/d; BP 143/87±2/2 mmHg); 10 with metoprolol succinate (M: 100 mg/d; 140/90±2/2 mmHg); and 10 with placebo (P; 139/85±2/2 mmHg). Before and after the drug intervention, forearm blood flow (FBF: plethysmography) was determined in response to intrabrachial infusion of the ETA selective receptor antagonist BQ123 and in combination with the ETB selective receptor antagonist BQ788.
Results: Subject baseline demographics (age, BMI, systolic and diastolic BP) were similar between the 3 groups. Blood pressure was lowered (P<0.05) to a similar extent by both N (128/77±2/2 mmHg) and M (127/77±3/2 mmHg) but unchanged by P (134/81±3/2 mmHg) treatment. Before the intervention, FBF increased by ~35% (P<0.05) in response to BQ123 and further increased ~65% above baseline following BQ788 (P<0.05) in all three groups. However, after N treatment the FBF response to BQ123 was 70% lower (P<0.05) and the response to BQ123+BQ788 was ~50% lower (P<0.05). In fact, after N treatment, the BQ123 infusion did not significantly alter resting FBF; suggesting an absence of ETA-mediated vasoconstrictor tone. In stark contrast, FBF responses to BQ123 and BQ123+BQ788 were not significantly altered by M treatment. As expected the vascular responses to ET-1 receptor blockade was not affect by P.
Conclusions: These results demonstrate that, in spite of a similar reduction in blood pressure, N, but not M, treatment reduces ET-1 vasoconstrictor tone in adults with elevated blood pressure. Diminished ET-1 mediated vasoconstrictor tone with N may provide an important vascular benefit in this at risk population.
Author Disclosures: B.L. Stauffer: Research Grant; Significant; Forest Laboratories, Inc.. K.J. Diehl: None. C.A. Dow: None. D.L. Templeton: None. J.J. Greiner: None. C.A. DeSouza: Research Grant; Significant; Forest Laboratories, Inc..
- © 2014 by American Heart Association, Inc.