Differential effects of nebivolol versus metoprolol on functional sympatholysis in hypertensive humans

Angela Price, Prafull Raheja, Zhongyun Wang, Debbie Arbique, Beverley Adams-Huet, Jere H. Mitchell, Ronald G. Victor, Gail Thomas, Wanpen Vongpatanasin

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

In young healthy humans, sympathetic vasoconstriction is markedly blunted during exercise to optimize blood flow to the metabolically active muscle. This phenomenon known as functional sympatholysis is impaired in hypertensive humans and rats by angiotensin II-dependent mechanisms, involving oxidative stress and inactivation of nitric oxide (NO). Nebivolol is a β1-adrenergic receptor blocker that has NO-dependent vasodilatory and antioxidant properties. We therefore asked whether nebivolol would restore functional sympatholysis in hypertensive humans. In 21 subjects with stage 1 hypertension, we measured muscle oxygenation and forearm blood flow responses to reflex increases in sympathetic nerve activity evoked by lower body negative pressure at rest, and during rhythmic handgrip exercise at baseline, after 12 weeks of nebivolol (5-20 mg/d) or metoprolol (100-300 mg/d), using a double-blind crossover design. We found that nebivolol had no effect on lower body negative pressure-induced decreases in oxygenation and forearm blood flow in resting forearm (from -29±5% to -30±5% and from -29±3% to -29±3%, respectively; P=NS). However, nebivolol attenuated the lower body negative pressure-induced reduction in oxygenation and forearm blood flow in exercising forearm (from -14±4% to -1±5% and from -15±2% to -6±2%, respectively; both P<0.05). This effect of nebivolol on oxygenation and forearm blood flow in exercising forearm was not observed with metoprolol in the same subjects, despite a similar reduction in blood pressure. Nebivolol had no effect on sympathetic nerve activity at rest or during handgrip, suggesting a direct effect on vascular function. Thus, our data demonstrate that nebivolol restored functional sympatholysis in hypertensive humans by a mechanism that does not involve β1-adrenergic receptors. CLINICAL TRIAL REGISTRATION - : URL: http://www.clinicaltrials.gov. Unique identifier: NCT01502787.

Original languageEnglish (US)
Pages (from-to)1263-1269
Number of pages7
JournalHypertension
Volume61
Issue number6
DOIs
StatePublished - Apr 3 2013

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Nebivolol
Metoprolol
Forearm
Lower Body Negative Pressure
Adrenergic Receptors
Nitric Oxide
Muscles
Adrenergic Antagonists
Vasoconstriction
Angiotensin II
Cross-Over Studies

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Price, A., Raheja, P., Wang, Z., Arbique, D., Adams-Huet, B., Mitchell, J. H., ... Vongpatanasin, W. (2013). Differential effects of nebivolol versus metoprolol on functional sympatholysis in hypertensive humans. Hypertension, 61(6), 1263-1269. https://doi.org/10.1161/HYPERTENSIONAHA.113.01302
Price, Angela ; Raheja, Prafull ; Wang, Zhongyun ; Arbique, Debbie ; Adams-Huet, Beverley ; Mitchell, Jere H. ; Victor, Ronald G. ; Thomas, Gail ; Vongpatanasin, Wanpen. / Differential effects of nebivolol versus metoprolol on functional sympatholysis in hypertensive humans. In: Hypertension. 2013 ; Vol. 61, No. 6. pp. 1263-1269.
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abstract = "In young healthy humans, sympathetic vasoconstriction is markedly blunted during exercise to optimize blood flow to the metabolically active muscle. This phenomenon known as functional sympatholysis is impaired in hypertensive humans and rats by angiotensin II-dependent mechanisms, involving oxidative stress and inactivation of nitric oxide (NO). Nebivolol is a β1-adrenergic receptor blocker that has NO-dependent vasodilatory and antioxidant properties. We therefore asked whether nebivolol would restore functional sympatholysis in hypertensive humans. In 21 subjects with stage 1 hypertension, we measured muscle oxygenation and forearm blood flow responses to reflex increases in sympathetic nerve activity evoked by lower body negative pressure at rest, and during rhythmic handgrip exercise at baseline, after 12 weeks of nebivolol (5-20 mg/d) or metoprolol (100-300 mg/d), using a double-blind crossover design. We found that nebivolol had no effect on lower body negative pressure-induced decreases in oxygenation and forearm blood flow in resting forearm (from -29±5{\%} to -30±5{\%} and from -29±3{\%} to -29±3{\%}, respectively; P=NS). However, nebivolol attenuated the lower body negative pressure-induced reduction in oxygenation and forearm blood flow in exercising forearm (from -14±4{\%} to -1±5{\%} and from -15±2{\%} to -6±2{\%}, respectively; both P<0.05). This effect of nebivolol on oxygenation and forearm blood flow in exercising forearm was not observed with metoprolol in the same subjects, despite a similar reduction in blood pressure. Nebivolol had no effect on sympathetic nerve activity at rest or during handgrip, suggesting a direct effect on vascular function. Thus, our data demonstrate that nebivolol restored functional sympatholysis in hypertensive humans by a mechanism that does not involve β1-adrenergic receptors. CLINICAL TRIAL REGISTRATION - : URL: http://www.clinicaltrials.gov. Unique identifier: NCT01502787.",
author = "Angela Price and Prafull Raheja and Zhongyun Wang and Debbie Arbique and Beverley Adams-Huet and Mitchell, {Jere H.} and Victor, {Ronald G.} and Gail Thomas and Wanpen Vongpatanasin",
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Price, A, Raheja, P, Wang, Z, Arbique, D, Adams-Huet, B, Mitchell, JH, Victor, RG, Thomas, G & Vongpatanasin, W 2013, 'Differential effects of nebivolol versus metoprolol on functional sympatholysis in hypertensive humans', Hypertension, vol. 61, no. 6, pp. 1263-1269. https://doi.org/10.1161/HYPERTENSIONAHA.113.01302

Differential effects of nebivolol versus metoprolol on functional sympatholysis in hypertensive humans. / Price, Angela; Raheja, Prafull; Wang, Zhongyun; Arbique, Debbie; Adams-Huet, Beverley; Mitchell, Jere H.; Victor, Ronald G.; Thomas, Gail; Vongpatanasin, Wanpen.

In: Hypertension, Vol. 61, No. 6, 03.04.2013, p. 1263-1269.

Research output: Contribution to journalArticle

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AU - Price, Angela

AU - Raheja, Prafull

AU - Wang, Zhongyun

AU - Arbique, Debbie

AU - Adams-Huet, Beverley

AU - Mitchell, Jere H.

AU - Victor, Ronald G.

AU - Thomas, Gail

AU - Vongpatanasin, Wanpen

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N2 - In young healthy humans, sympathetic vasoconstriction is markedly blunted during exercise to optimize blood flow to the metabolically active muscle. This phenomenon known as functional sympatholysis is impaired in hypertensive humans and rats by angiotensin II-dependent mechanisms, involving oxidative stress and inactivation of nitric oxide (NO). Nebivolol is a β1-adrenergic receptor blocker that has NO-dependent vasodilatory and antioxidant properties. We therefore asked whether nebivolol would restore functional sympatholysis in hypertensive humans. In 21 subjects with stage 1 hypertension, we measured muscle oxygenation and forearm blood flow responses to reflex increases in sympathetic nerve activity evoked by lower body negative pressure at rest, and during rhythmic handgrip exercise at baseline, after 12 weeks of nebivolol (5-20 mg/d) or metoprolol (100-300 mg/d), using a double-blind crossover design. We found that nebivolol had no effect on lower body negative pressure-induced decreases in oxygenation and forearm blood flow in resting forearm (from -29±5% to -30±5% and from -29±3% to -29±3%, respectively; P=NS). However, nebivolol attenuated the lower body negative pressure-induced reduction in oxygenation and forearm blood flow in exercising forearm (from -14±4% to -1±5% and from -15±2% to -6±2%, respectively; both P<0.05). This effect of nebivolol on oxygenation and forearm blood flow in exercising forearm was not observed with metoprolol in the same subjects, despite a similar reduction in blood pressure. Nebivolol had no effect on sympathetic nerve activity at rest or during handgrip, suggesting a direct effect on vascular function. Thus, our data demonstrate that nebivolol restored functional sympatholysis in hypertensive humans by a mechanism that does not involve β1-adrenergic receptors. CLINICAL TRIAL REGISTRATION - : URL: http://www.clinicaltrials.gov. Unique identifier: NCT01502787.

AB - In young healthy humans, sympathetic vasoconstriction is markedly blunted during exercise to optimize blood flow to the metabolically active muscle. This phenomenon known as functional sympatholysis is impaired in hypertensive humans and rats by angiotensin II-dependent mechanisms, involving oxidative stress and inactivation of nitric oxide (NO). Nebivolol is a β1-adrenergic receptor blocker that has NO-dependent vasodilatory and antioxidant properties. We therefore asked whether nebivolol would restore functional sympatholysis in hypertensive humans. In 21 subjects with stage 1 hypertension, we measured muscle oxygenation and forearm blood flow responses to reflex increases in sympathetic nerve activity evoked by lower body negative pressure at rest, and during rhythmic handgrip exercise at baseline, after 12 weeks of nebivolol (5-20 mg/d) or metoprolol (100-300 mg/d), using a double-blind crossover design. We found that nebivolol had no effect on lower body negative pressure-induced decreases in oxygenation and forearm blood flow in resting forearm (from -29±5% to -30±5% and from -29±3% to -29±3%, respectively; P=NS). However, nebivolol attenuated the lower body negative pressure-induced reduction in oxygenation and forearm blood flow in exercising forearm (from -14±4% to -1±5% and from -15±2% to -6±2%, respectively; both P<0.05). This effect of nebivolol on oxygenation and forearm blood flow in exercising forearm was not observed with metoprolol in the same subjects, despite a similar reduction in blood pressure. Nebivolol had no effect on sympathetic nerve activity at rest or during handgrip, suggesting a direct effect on vascular function. Thus, our data demonstrate that nebivolol restored functional sympatholysis in hypertensive humans by a mechanism that does not involve β1-adrenergic receptors. CLINICAL TRIAL REGISTRATION - : URL: http://www.clinicaltrials.gov. Unique identifier: NCT01502787.

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