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 [3H]norepinephrine (NE), ANG II (10 nM) resulted in an increase (3-fold) in evoked 3H overflow from ISF slices from cold-exposed rats compared with ambient temperature controls. However, although basal 3H outflow was increased (2-fold) in ISF slices from cold-exposed rats, evoked 3H overflow was not different between ISF slices from cold-exposed and control rats. Specific neuronal uptake of [3H]NE in ISF slices from cold-exposed rats was decreased by 64%. Administration of the non-peptide AT1-receptor antagonist losartan to cold-exposed rats resulted in complete inhibition of ANG II-mediated presynaptic facilitation of evoked 3H overflow from ISF slices. However, losartan administration had no effect on cold-induced increases in ANG II content, protein content, and decreases in neuronal [3H]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.
Cassis
L A
LA
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
D000064:Acclimatization; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001833:Body Temperature Regulation; D003080:Cold Temperature; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013599:Systole / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*; D014316:Tritium
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D014316:Tritium; D000804:Angiotensin II; D012083:Renin; D019808:Losartan; D009638:Norepinephrine