Effects of desmethylimipramine and normetanephrine on calorigenic response and plasma noradrenaline concentration in warm- and in cold-acclimated rats exposed to cold

Oxygen consumption and plasma noradrenaline concentration were increased significantly above resting levels in warm-acclimated and in cold-acclimated rats exposed to an ambient temperature of 4 °C. Administration of normetanephrine (1 μg∙min−1∙g body weight−0.74), but not of desmethylimipramine (1 mg∙kg−1), resulted in higher resting plasma noradrenaline levels at 24 °C and increased the length of time required for the oxygen consumption to return to resting levels after cold exposure in both acclimation groups. These observations support a significant role of extraneuronal uptake in noradrenaline inactivation under normal physiological conditions. Calorigenic responses to cold exposure were not affected at all by treatment of animals with desmethylimipramine and (or) normetanephrine in either warm-acclimated or cold-acclimated rats, although an enhancing effect of these uptake inhibitors on plasma noradrenaline was evident in cold-acclimated rats. It is suggested that a peripheral–central thermoregulatory mechanism adjusts activation of thermogenic effectors so as to maintain a steady calorigenic response, appropriate to the thermal demand of the environment, to compensate for changes in perineuronal concentration of noradrenaline in sympathetic thermoeffectors owing to blockade of extraneuronal uptake.