Alpha 2-adrenoceptor-mediated effects on resting energy expenditure

The effects of the alpha 2-adrenoceptor agonist guanfacin, other alpha-adrenoceptor agonists, beta-adrenoceptor agonists and alpha- and beta-adrenoceptor antagonists on resting energy expenditure (REE) were studied in female Wistar rats at 23 degrees C. Guanfacin produced a maximum change of -20% (-1.2 W/kg0.75, P < 0.001) in REE in rats with a mean +/- s.d. pre-treatment REE of 6.0 +/- 0.9 W/kg0.75. The dose producing half the maximum effect was 0.4 mg/kg. Other alpha 2-adrenoceptor agonists, clonidine, UK14304 and the peripherally acting alpha 2-agonist, p-aminoclonidine, also decreased REE. The effects of guanfacin were antagonized by idazoxan, yohimbine and RX821002 (all selective for alpha 2-adrenoceptors) but not prazosin (selective for alpha 1-adrenoceptors). Prazosin used alone lowered REE indicating a role for alpha 1-adrenoceptors in normal REE. To determine whether guanfacin was acting directly on oxygen-consuming tissues or if it was acting by lowering sympathetic tone, rats were treated with selective beta 1-, beta 2- and beta 3-agonists and antagonists both alone and in combination with guanfacin. The results of these experiments support the hypothesis that guanfacin lowered REE through a decrease in sympathetic tone (noradrenaline release) which in turn lessened the normal resting stimulation of alpha 1- and beta 1-adrenoceptors.