Effects of cardioselective and nonselective beta-adrenergic blockade on the performance of highly trained runners

Anderson, Richard L.; Wilmore, Jack H.; Joyner, Michael J.; Freund, B. J.; Hartzell, Albert A.; Todd, Carl A.; Ewy, Gordon A.

doi:10.1016/0002-9149(85)91072-0

Cited by 38 publications

(22 citation statements)

References 38 publications

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“…Treatment with older generation ␤-AR blockers is associated with exercise intolerance and fatigue (1,19,29). Although this is thought to be due to attenuation of the ␤-AR-mediated increase in HR and cardiac output during exercise, our study demonstrated another potential mechanism of selective impair- ment in the skeletal muscle microvascular function, which was independent of cardiac output and conduit artery tone.…”

Section: Perspectivesmentioning

confidence: 60%

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

Velasco

Solow

Price

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Use of ␤-adrenergic receptor (AR) blocker is associated with increased risk of fatigue and exercise intolerance. Nebivolol is a newer generation ␤-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 Ϯ 2.6/81.7 Ϯ 1.8 vs. 131.6 Ϯ 2.7/80.8 Ϯ 1.5 mmHg and 63 Ϯ 2 vs. 64 Ϯ 2 beats/min) compared with baseline (142.1 Ϯ 2.0/88.7 Ϯ 1.4 mmHg and 75 Ϯ 2 beats/min, respectively, both P Ͻ 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 Ͻ 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.exercise; sympathetic nervous system; muscle blood flow; hypertension NEW & NOTEWORTHYWe identified a deleterious effect of chronic administration of metoprolol on microvascular function during handgrip in hypertensive patients, which was not observed with nebivolol. The impaired muscle capillary recruitment during exercise may predispose to development of exercise intolerance.PREVIOUS STUDIES DEMONSTRATED impaired muscle capillary recruitment in hypertension (8, 12), possibly related to impaired microvascular function or capillary rarefaction (27,28). In hypertensive patients, both metoprolol and propranolol can further impair microvascular function by acutely reducing resting capillary blood flow in the skeletal muscle (22, 23), which may predispose to development of exercise intolerance or fatigue. Nebivolol is a third-generation ␤-adrenergic receptor (AR) blocker that also possesses vasodilator properties (35). The vasodilator effect is attributed to partly due to the antioxidant effect via inhibition of NADPH oxidase activity or reduced expression of the NADPH oxidase subunits p47 phox (18,20, 35). However, the chronic effect of either older or newer generation ␤-AR blockers on microvascular function during exercise and endothelial cell (EC) expression of the p47 phox N...

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Section: Perspectivesmentioning

confidence: 60%

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

Velasco

Solow

Price

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…Use of older generation β-blockers without ancillary vasodilating properties is associated with exercise intolerance and fatigue 30–32 . This is thought to be due to attenuation of β-AR mediated increase in heart rate and cardiac output during exercise 32 .…”

Section: Discussionmentioning

confidence: 99%

“…This is thought to be due to attenuation of β-AR mediated increase in heart rate and cardiac output during exercise 32 . These side effects appear to be much less common in patients treated with newer generation β-blockers like nebivolol due to its tendency to improve oxygen uptake or augment the reduction in systemic vascular resistance at peak exercise 31, 33 .…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Nebivolol Versus Metoprolol on Functional Sympatholysis in Hypertensive Humans

et al. 2013

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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 if nebivolol would restore functional sympatholysis in hypertensive humans. In 21 subjects with stage I hypertension, we measured muscle oxygenation and forearm blood flow (FBF) responses to reflex increases in sympathetic nerve activity (SNA) evoked by lower body negative pressure (LBNP) at rest and during rhythmic handgrip exercise at baseline, after 12 weeks of nebivolol (5–20 mg/day), or metoprolol (100–300 mg/day), using a double-blind crossover design. We found that nebivolol had no effect on LBNP-induced decreases in oxygenation and FBF in resting forearm (from −29±5 to −30±5% and from −29±3 to −29±3%, respectively; p=NS). However, nebivolol attenuated the LBNP-induced reduction in oxygenation and FBF 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 FBF in exercising forearm was not observed with metoprolol in the same subjects despite a similar reduction in BP. Nebivolol had no effect on SNA 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.

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“…max following @B (Reybrouck et al 1977;Wilmore et al 1985;SUar et al 1982). Similarly, although some studies suggest that PB significantly reduces oxygen uptake (V%) during submaximal exercise (Pearson et al 1979;Tesch and Kaiser 1983;Anderson et al 1985;Frisk-Holmberg et al 1985), other studies have demonstrated no change (Wilmore et al 1985;Franz et al 1985;Van Hemaarden et al 1979). …”

Section: Introductionmentioning

confidence: 99%

Factors contributing to increased muscle fatigue with β-blockers

McKelvie¹,

Jones²,

Heigenhauser³

1991

Can. J. Physiol. Pharmacol.

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beta-Adrenoceptor blockers are widely used clinically and can be classified as nonselective (beta 1 and beta 2) or selective (beta 1). Impairment of exercise performance is a well-known side effect of this group of drugs. This paper reviews mechanisms that could potentially be responsible for this impairment. In addition to cardiovascular and metabolic effects, beta-blockade inhibits Na(+)-K+ ATPase pumps controlling ion movement between muscle and plasma and thus may contribute to muscle fatigue through this mechanism. To investigate the relationship between the change in plasma [K+] and exercise performance, we studied healthy male subjects taking propranolol. Eight subjects performed maximal incremental cycle ergometer exercise tests during control (no drug), low dose (LD) (40 mg daily), and high dose (HD) (265 +/- 4.3 (SE) mg daily) of propranolol. The control plasma [K+] (5.8 +/- 0.12 mequiv./L) during exercise was significantly lower than either the LD (6.4 +/- 0.05 mequiv./L) or HD (6.1 +/- 0.16 mequiv./L) values. There was no significant difference between plasma [K+] for the LD and HD of propranolol. However, maximum oxygen uptake was reduced only while taking the HD of propranolol. Six of the subjects also performed three 30-s bouts of high intensity exercise on an isokinetic cycle ergometer while taking the LD and HD of propranolol. There was no significant difference between doses for the increase in plasma [K+] (LD, 7.8 +/- 0.35 mequiv./L vs. HD, 7.6 +/- 0.36 mequiv./L) during exercise. However, exercise performance was significantly reduced during HD compared with LD. These results suggest that the increases in plasma [K+] with propranolol did not play a direct significant role in the reduced performance observed during the HD.

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Effects of cardioselective and nonselective beta-adrenergic blockade on the performance of highly trained runners

Cited by 38 publications

References 38 publications

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

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

Differential Effects of Nebivolol Versus Metoprolol on Functional Sympatholysis in Hypertensive Humans

Factors contributing to increased muscle fatigue with β-blockers

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