Yohimbine Attenuates Baroreflex-Mediated Bradycardia in Humans

Abstract

α-2 Adrenoreceptor stimulation profoundly augments baroreflex-mediated bradycardia presumably through parasympathetic activation. We tested the hypothesis that endogenous α-2 adrenergic tone mediates a similar response. In 10 healthy men (age: 33±3 years; body mass index: 24±1.3 kg/m 2 ), we determined baroreflex control of heart rate and sympathetic traffic after ingestion of the selective α-2 adrenoceptor antagonist yohimbine (20 mg) or placebo. Testing was conducted in a randomized, double-blind, crossover fashion. We measured heart rate, brachial and finger blood pressure, and muscle sympathetic nerve activity. Sympathetic and parasympathetic baroreflex curves were determined using incremental phenylephrine and nitroprusside infusions (0.3, 0.6, 0.9, 1.2, and 1.5 μg/kg per minute). Plasma norepinephrine increased with yohimbine (50±38 ng/L; P <0.05) and was unchanged with placebo (2.2±7.6 ng/L). Blood pressure increased 13±4/8±1 mm Hg with yohimbine and 6±2/3±1 mm Hg with placebo ( P <0.01). HR increased 5±1 bpm with yohimbine but did not change with placebo ( P <0.01). Ninety minutes after drug ingestion, resting muscle sympathetic nerve activity was similar with yohimbine and with placebo. Baroreflex control of heart rate was decreased with yohimbine (6 ms/mm Hg versus 10 ms/mm Hg; P <0.01) and reset to higher blood pressure and heart rate values. In contrast, yohimbine did not alter the sympathetic baroreflex curve. Yohimbine selectively attenuates baroreflex heart rate control in normotensive young men possibly through parasympathetic mechanisms.