Comparison of Nebivolol and Metoprolol With Exercise and Angiotensin II in Hypertensive Patients
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension) |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 6/10/2018 |
| Start Date: | April 2009 |
| End Date: | June 2013 |
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.
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.
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.
Inclusion Criteria:
- Stage I hypertension (140-159/90-99 mmHg)
- Men and women age 18-65
Exclusion Criteria:
- Congestive heart failure or coronary artery disease
- Blood pressure averaging >159/99 mmHg or resting heart rate < 55 bpm
- Serum creatinine > 1.4 mg/dL
- Asthma or chronic obstructive pulmonary diseases
- Left ventricular hypertrophy by echocardiography or ECG
- Pregnancy
- Hypersensitivity to beta blockers, microbubble contrast agents, or angiotensin
- Any history of substance abuse (other than tobacco)
- Concomitant drug treatment which raises endogenous nitric oxide levels such as
nitrates or phosphodiesterase V inhibitors (Viagra, Levitra, or Cialis)
- History of symptomatic bradycardia or heart block
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