ROLE OF ANGIOTENSIN-II IN BROWN ADIPOSE THERMOGENESIS DURING COLD-ACCLIMATION

The role of angiotensin II (ANG II) in increased sympathetic neuroeffector mechanisms observed in cold-induced thermogenesis of brown adipose tissue (BAT) was examined. Cold exposure (4-degrees-C) for 7 days resulted in an increase in interscapular fat (ISF) ANG II content expressed per gram wet weight or per lobe of ISF, without concomitant changes in plasma components of the renin-angiotensin system. Additionally, in ISF slices preloaded with [H-3]norepinephrine (NE), ANG II (10 nM) resulted in an increase (3-fold) in evoked H-3 overflow from ISF slices from cold-exposed rats compared with ambient temperature controls. However, although basal H-3 outflow was increased (2-fold) in ISF slices from cold-exposed rats, evoked H-3 overflow was not different between ISF slices from cold-exposed and control rats. Specific neuronal uptake of [H-3]NE in ISF slices from cold-exposed rats was decreased by 64%. Administration of the nonpeptide AT1-receptor antagonist losartan to cold-exposed rats resulted in complete inhibition of ANG II-mediated presynaptic facilitation of evoked H-3 overflow from ISF slices. However, losartan administration had no effect on cold-induced increases in ANG II content, protein content, and decreases in neuronal [H-3]NE uptake in ISF. Results from these studies suggest that cold-induced thermogenesis of BAT results in alterations in presynaptic ANG II facilitation of NE release and defects in removal of NE from the synaptic cleft (neuronal uptake), both of which would enhance sympathetic nervous system-mediated thermogenesis. Furthermore, these results demonstrate a role for ANG II in enhanced sympathetic activity of cold-induced thermogenesis in BAT.