Differential effects of nebivolol vs. metoprolol on microvascular function in hypertensive humans

Am J Physiol Heart Circ Physiol. 2016 Jul 1;311(1):H118-24. doi: 10.1152/ajpheart.00237.2016. Epub 2016 May 13.

Abstract

Use of β-adrenergic receptor (AR) blocker is associated with increased risk of fatigue and exercise intolerance. Nebivolol is a newer generation β-blocker, which is thought to avoid this side effect via its vasodilating property. However, the effects of nebivolol on skeletal muscle perfusion during exercise have not been determined in hypertensive patients. Accordingly, we performed contrast-enhanced ultrasound perfusion imaging of the forearm muscles in 25 untreated stage I hypertensive patients at rest and during handgrip exercise at baseline or after 12 wk of treatment with nebivolol (5-20 mg/day) or metoprolol succinate (100-300 mg/day), with a subsequent double crossover for 12 wk. Metoprolol and nebivolol each induced a reduction in the resting blood pressure and heart rate (130.9 ± 2.6/81.7 ± 1.8 vs. 131.6 ± 2.7/80.8 ± 1.5 mmHg and 63 ± 2 vs. 64 ± 2 beats/min) compared with baseline (142.1 ± 2.0/88.7 ± 1.4 mmHg and 75 ± 2 beats/min, respectively, both P < 0.01). Metoprolol significantly attenuated the increase in microvascular blood volume (MBV) during handgrip at 12 and 20 repetitions/min by 50% compared with baseline (mixed-model P < 0.05), which was not observed with nebivolol. Neither metoprolol nor nebivolol affected microvascular flow velocity (MFV). Similarly, metoprolol and nebivolol had no effect on the increase in the conduit brachial artery flow as determined by duplex Doppler ultrasound. Thus our study demonstrated a first direct evidence for metoprolol-induced impairment in the recruitment of microvascular units during exercise in hypertensive humans, which was avoided by nebivolol. This selective reduction in MBV without alteration in MFV by metoprolol suggested impaired vasodilation at the precapillary arteriolar level.

Trial registration: ClinicalTrials.gov NCT01501929.

Keywords: exercise; hypertension; muscle blood flow; sympathetic nervous system.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists / adverse effects
  • Adrenergic beta-1 Receptor Antagonists / therapeutic use*
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Cross-Over Studies
  • Endothelial Cells / enzymology
  • Female
  • Forearm
  • Hand Strength
  • Humans
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / enzymology
  • Hypertension / physiopathology
  • Male
  • Metoprolol / adverse effects
  • Metoprolol / therapeutic use*
  • Microcirculation / drug effects*
  • Microvessels / drug effects*
  • Microvessels / enzymology
  • Microvessels / physiopathology
  • Middle Aged
  • Muscle Contraction
  • Muscle Fatigue
  • Muscle, Skeletal / blood supply*
  • NADPH Oxidases / metabolism
  • Nebivolol / adverse effects
  • Nebivolol / therapeutic use*
  • Perfusion Imaging / methods
  • Regional Blood Flow
  • Texas
  • Treatment Outcome
  • Ultrasonography
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / therapeutic use*

Substances

  • Adrenergic beta-1 Receptor Antagonists
  • Antihypertensive Agents
  • Vasodilator Agents
  • Nebivolol
  • NADPH Oxidases
  • neutrophil cytosolic factor 1
  • Metoprolol

Associated data

  • ClinicalTrials.gov/NCT01501929