title: The role of nitric oxide in remodeling of capillary network in rat interscapular brown adipose tissue after long-term cold acclimation.
abstract: Cold exposure has been shown to increase blood flow in interscapular brown adipose tissue (IBAT). The aim of the present study was to evaluate the role of the L-arginine-nitric oxide (*NO) pathway on IBAT capillary network remodeling and its possible correlation with superoxide anion radical (O2(*-)). In the rats that received L-arginine (2.25%) or NG-nitro-L-arginine methyl ester (L-NAME, 0.01%) as a drinking liquid and maintained at room (22+/-1 degrees C) or low (4+/-1 degrees C) temperature for 45 days, IBAT capillaries were analyzed by stereology and observed by light and electron microscopy. Additionally, endothelial *NO synthase (eNOS) expression, nitrotyrosine immunoreactivity and both copper zinc superoxide dismutase (CuZnSOD) enzyme activity and immunohistochemical localization were examined. Stereological analyses of IBAT show that the capillary volume density, as well as capillary-to-brown adipocytes ratio, are increased in cold. L-arginine treatment increases, while L-NAME decreases both parameters, compared to respective controls. Those changes were accompanied by capillary dilatation observed by light and electron microscopy. The activity of CuZnSOD is lower in control cold-acclimated rats, as well as in both L-arginine-treated groups, when compared to control animals acclimated to room temperature. L-NAME treatment attenuates the effects both of cold and L-arginine on CuZnSOD and increases immunopositivity for CuZnSOD in room temperature-acclimated rats. Our results show that *NO induces remodeling of the IBAT capillary network by angiogenesis, and presumably that interaction with O2(*-) has a role in that modulation. The increased eNOS expression accompanied by an increased nitrotyrosine immunoreaction observed in both L-arginine-treated groups compared to corresponding controls strengthens this hypothesis.
authors.affiliation: Institute of Zoology, Faculty of Biology, University of Belgrade, Belgrade, Serbia. sankor@bf.bio.bg.ac.yu
authors.forename: A
authors.initials: A
authors.lastname: Korac
authors.forename: B
authors.initials: B
authors.lastname: Buzadzic
authors.forename: V
authors.initials: V
authors.lastname: Petrovic
authors.forename: A
authors.initials: A
authors.lastname: Vasilijevic
authors.forename: A
authors.initials: A
authors.lastname: Jankovic
authors.forename: K
authors.initials: K
authors.lastname: Micunovic
authors.forename: B
authors.initials: B
authors.lastname: Korac
mesh_terms: D000064:Acclimatization; D002001:Adipose Tissue, Brown / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002196:Capillaries / Q000187:drug effects / Q000648:ultrastructure; D003080:Cold Temperature; D007150:Immunohistochemistry; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats / Q000502:physiology*; D013223:Statistics as Topic; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester