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Effect of the α2‐Adrenergic Antagonist Yohimbine on Orthostatic Tolerance

We studied the effect of yohimbine, a drug that inhibits presynaptic Oj-adrenergic receptors and increases the neuronal release of norepinephrine from the central and sympathetic nervous systems, on tolerance to cardiovascular stress in 10 untrained, healthy subjects. Using radioligand binding of tritiated yohimbine to platelets, these subjects were found to have a normal complement of a<2-adrenergic receptors (174±18 [±SM] receptors/platelet) with normal X, (1.93±0.17 nmol/1). Lower body negative pressure was used to test responses to cardiovascular stress in the subjects after they received either placebo or 20 mg yohimbine. Graded lower body negative pressure from 0 to −40 mm Hg significantly decreased systolic blood pressure from 116±3.7 to 106±5.8 mm Hg, increased heart rate from 54±3 to 68±7 beats/min, decreased forearm blood flow from 1.8 ±0.21 to 1.36±0.25 ml/100 ml/min, and increased forearm vascular resistance from 55.76±12.1 to 77.26±15.8 mm Hg/ml/min. Yohimbine increased the blood pressure at rest and during lower body negative pressure, but these changes were not significantly different from values recorded from the individuals when they were given placebo. Compared with placebo, however, yohimbine significantly increased forearm blood flow at rest (1.80±0.21 vs. 2.66±OJ1 ml/100 ml/min, p < 0.05) and during −40 mm Hg of lower body negative pressure (U6±0.25 vs. 1.91±0.28 ml/100 ml/min, p < 0.05). We also found that yohimbine significantly increased the plasma insulin concentration in these fasted subjects (9.4±2.4 vs. 14.5±1.4 ng/ml,/?<0.05) without inducing hypoglycemia. Because this agent increases forearm blood flow, yohimbine might be useful in treating the orthostatic hypotension and ischemic vascular disease that results from the autonomic insufficiency common in patients with diabetes mellitus.