Yohimbine administration prevents over-responsiveness to epinephrine induced by simulated microgravity

Abstract

Background: Simulated microgravity produces sustained inhibition of sympathoneural release, turnover, and synthesis of norepinephrine (NE) and hypersensitization of beta-adrenergic pathways. These changes may explain the orthostatic intolerance experienced by astronauts returning from spaceflights.

Hypothesis: Chronic administration of yohimbine would prevent the increase of beta-adrenergic hypersensitivity to epinephrine (Epi) induced by simulated microgravity.

Methods: Eight healthy young subjects received 8 mg of yohimbine (an antagonist of alpha2adrenoceptors) orally twice a day during the simulated microgravity achieved through -6 degrees head-down bed rest (HDBR). The catecholamine-induced lipolysis was studied on isolated fat cells from subcutaneous adipose tissue before HDBR and on the fifth day of HDBR. Epi was infused at three graded rates (0.01, 0.02, and 0.03 microg x kg(-1) x min(-1) for 40 min each) before and at the end of the HDBR period. The effects of Epi on the sympathetic nervous system (SNS) activity-assessed by plasma NE levels and spectral analysis of systolic BP and heart rate variability-and on plasma levels of glycerol, non-esterified fatty acids, glucose, and insulin and on energy expenditure were evaluated.

Results: Under yohimbine treatment, HDBR failed to modify urinary NE excretion and spectral variability of systolic BP in the mid-frequency range. The beta- and alpha-adrenergic sensitivity of fat cells were not modified by HDBR nor were plasma NE levels and spectral variability of systolic BP induced by Epi infusion. No alteration of Epi-induced changes in heart rate and systolic and diastolic BPs were observed after HDBR. Epi-induced increases in plasma glucose, insulin, glycerol, and non-esterified fatty acid levels as well as energy expenditure were also unmodified by HDBR. Only the Epi-induced plasma lactate level was increased by HDBR.

Conclusion: Our data suggest that the increase in the effects of Epi induced during microgravity could be attenuated by chronic administration of yohimbine. An explanation for this effect could be SNS activation brought about by the alpha2-adrenoceptor antagonist properties of yohimbine.