Effect of the alpha 2-adrenergic antagonist yohimbine on orthostatic tolerance.

Abstract

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 [±S£M] 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 -4 0 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. (Hypertension 1990;15:877-880) T he a-adrenergic receptors are found on presynaptic neurons of the central nervous system, the peripheral nervous system, and blood vessels. The a,-adrenergic receptors are found mainly on blood vessels, and when stimulated by endogenous ligands such as norepinephrine, cause vascular smooth muscle to contract and vascular resistance and blood pressure to increase. The a 2 -adrenergic receptors are found on platelets, in the vasculature, and on presynaptic neurons. Activation of presynaptic a 2 -adrenergjc receptors results in a decrease in catecholamine release from nerve terminals and the adrenal medulla and a decrease in blood pressure. Alternatively, antagonism Because increasing circulating and central catecholamines increases blood pressure, we hypothesized that pharmacological agents that increase catecholamine release could increase tolerance to cardiovascular stress experienced by patients with orthostatic hypotension or by fighter pilots who experience increased gravitational force (+Gz). We measured the effect of the oral a 2 -adrenergic receptor antagonist yohimbine on the blood pressure response to the unloading of cardiovascular baroreceptors with graded lowe...

Mechanism of Epinephrine-Induced Platelet Aggregation

“…A2AR receptor binding and number were determined as described previously 4 with Scatchard analysis of [ 3 H]yohimbine binding to platelets incubated in different buffers. Briefly, platelets were isolated after centrifugation of 10 mL of PRP.…”

Endurance Exercise Training in Orthostatic Intolerance

“…5 Management of patients with OI is difficult. An increase in blood volume by higher intake of fluid and salt, 4 as well as the use of ␤-blockers 6 and yohimbine, 7 have been suggested.…”

Ephedra alkaloids inhibit platelet aggregation

“…We have shown that pharmacologic inhibition of the vascular a-2 adrenergic receptors results in an increase in peripheral blood flow in humans [22]. However, inhibition of central, presynaptic a-2 adrenergic receptors also results in increases in circulating catecholamines that, depending on the relative complement of vascular a-1/a-2 receptors, raises BP.…”