Effects of Nebivolol Versus Metoprolol on Blood Flow Responses to Exercise and Angiotensin II in Hypertensive Patients
Effects of Nebivolol Versus Metoprolol on Blood Flow Responses to Exercise and Angiotensin II in Hypertensive Patients
The purpose of this study is to determine if Nebivolol a) attenuates the angiotensin II (Ang II)-induced increase in oxidative stress, thereby attenuating Ang II-induced vasoconstriction; and b) attenuates sympathetic mediated vasoconstriction during exercise, thereby reducing functional skeletal muscle ischemia in hypertensive patients.
In 40 untreated, stage I hypertensive subjects, Investigators will measure sympathetic nerve activity (microneurography); total forearm blood flow (high-resolution ultrasonography); skeletal muscle oxygenation (Near Infrared spectroscopy); plasma F2-isoprostanes; cardiac output (non-invasive impedance plethysmography); and blood pressure at baseline and after a) rhythmic handgrip exercise at 30% of maximal voluntary contraction alone for 3 minutes, b) rhythmic handgrip at the same intensity of exercise plus lower body negative pressure (LBNP) to activate sympathetic nerve activity (SNA) for 2 minutes, and c) during intravenous infusion of Angiotensin II at the dose of 1, 2, and 3 ng/kg/min for 15 minutes at each dose.
Each subject will then be randomized to receive 12 weeks of Nebivolol (Bystolic, 5-20 mg/day) or Metoprolol Succinate (Toprol XL, 100-300 mg/day), using a randomized crossover design. There will be a 2-week washout period between the two treatment periods. During drug treatment, blood pressure will be monitored every 4 weeks and the doses of Nebivolol and Metoprolol will be titrated to keep BP <140/90 mmHg. SNA, total forearm blood flow, skeletal muscle blood flow, muscle oxygenation, cardiac output, and blood pressure responses to Nebivolol will be compared to responses during Metoprolol in the same subjects.
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Exclusion Criteria: