Abstract

The hypothesis that celiprolol, a i¢-1 adrenoceptor antagonist with the ancillary property of i¢-2 mediated vasodilation, would increase blood flow to active muscles during exercise and result in less impairment of exercise performance, compared with the i¢-1 antagonist atenolol was tested. After an initial 3 weeks washout phase, 11 untrained hypertensive men participated in a 6 week crossover study of the two drugs. Each treatment phase was followed by a 3 week placebo phase. Resting forearm and calf vascular resistance measured by venous occlusion plethysmography and submaximal and maximal bicycle ergometer exercise responses were evaluated at the end of each treatment and placebo phase. Celiprolol significantly decreased resting forearm and calf vascular resistance whereas atenolol had no significant effect. Neither i¢-blocker significantly affected submaximal exercise oxygen uptake, rate of perceived exertion, minute ventilation, or respiratory exchange ratio. Both i¢-blockers significantly and similarly decreased peak oxygen uptake; celiprolol 23.9 ±1.7, atenolol 24.9 ± 1.7, placebo 27.3 ± 1.3 ml/kg/min. These findings suggest that during exercise while on i¢-blockade, other factors such as sympathetic vasoconstriction or local metabolic vasodilation may override β-2-mediated vasodilation. Thus, the addition of β-2 agonist to β-1 antagonism decreases resting vascular resistance, but offers no advantage over conventional β-1 blockade therapy during exercise. Key words: Celiprolol, atenolol, oxygen uptake, venous occlusion plethysmography, bicycle ergometer, β-blocker, blood flow, vascular resistance.

Highlights

  • The primary hemodynamic disturbance in individuals with established hypertension is elevated peripheral resistance with normal or low cardiac output (Folklow, 1982; Freis, 1960)

  • Celiprolol had no effect on pre-exercise heart rates (HR) whereas atenolol produced a significant decrease compared with placebo

  • This study examined peripheral blood flow and exercise responses in untrained middle-aged hypertensive males following chronic administration of celiprolol, atenolol, or placebo

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Summary

INTRODUCTION

The primary hemodynamic disturbance in individuals with established hypertension is elevated peripheral resistance with normal or low cardiac output (Folklow, 1982; Freis, 1960). Peripheral vascular resistance decreases but not to the same extent as in individuals who are normotensive cardiac output is generally subnormal during exercise (Lund-Johansen, 1980). Treatment of hypertension with β-adrenergic blocking agents usually effectively lowers blood pressure (BP), this class of drug does not improve the hemodynamic profile of these patients either at rest or during exercise. It has been postulated that a reduced cardiac output and increased total peripheral resistance could contribute to inadequate blood flow to the active muscles and early onset of fatigue during exercise. This study was designed to test the hypothesis that celiprolol, compared with the β-1 receptor antagonist atenolol, would allow more blood flow to the active muscles and produce less slowing of heart rate during exercise, resulting in less submaximal fatigue and a higher peak exercise capacity

METHODOLOGY
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DISCUSSION

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