title: Alterations of myocardial sympathetic innervation in response to hypoxia.
abstract: The effects of altitude hypoxia on myocardial sympathetic nerve function were assessed in rats using metaiodobenzylguanidine (MIBG).
  
  
  METHODS
  To estimate the change in uptake-1 function induced by hypoxia, three sets of rats were submitted to 5-, 7- and 21-day hypoxia (hypobaric chamber at 410 Torr) and one set of control rats was injected with 25 muCi of 123I-MIBG. Four hours later, the rats were killed and 123I activity was counted in both ventricles. The proportion of MIBG fixed in the myocardium through the norepinephrine (NE) transporter (uptake-1) was evaluated indirectly in 5-day hypoxic and controls rats by the injection of desipramine before 123I-MIBG administration. Myocardial perfusion was evaluated in 5-day hypoxic rats and controls by 201Tl injection.
  
  
  RESULTS
  Myocardial 123I-MIBG activity was 0.253% +/- 0.036% kg dose/g-1 in controls and was decreased (0.188% +/- 0.029% kg dose/g-1, p = 0.001) in 5-day hypoxic rats. This decrease was not related to a change in cardiac perfusion. The decrease in MIBG uptake existed before the appearance of cardiac hypertrophy. Desipramine decreased MIBG uptake by 48% in controls and 17% in hypoxic rats, suggesting that the decrease predominantly affected MIBG uptake by the NE transporter.
  
  
  CONCLUSIONS
  Chronic hypoxia leads to a decrease in myocardial NE-uptake-1 function. This finding suggests that altered tissue oxygen supply could play a role in the decreased cardiac MIBG uptake reported in human cardiomyopathies.
authors.affiliation: Department of Medical Research, Service Hospitalier Frédéric Joliot, DSV-CEA, Orsay, France.
authors.forename: M
authors.initials: M
authors.lastname: Scherrer-Crosbie
authors.forename: K
authors.initials: K
authors.lastname: Mardon
authors.forename: J
authors.initials: J
authors.lastname: Cayla
authors.forename: A
authors.initials: A
authors.lastname: Syrota
authors.forename: P
authors.initials: P
authors.lastname: Merlet
mesh_terms: D019797:3-Iodobenzylguanidine; D018759:Adrenergic Uptake Inhibitors; D000532:Altitude Sickness / Q000000981:diagnostic imaging* / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000000981:diagnostic imaging* / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003891:Desipramine; D006321:Heart / Q000294:innervation*; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013565:Sympatholytics; D027981:Symporters
chemical_list: D018759:Adrenergic Uptake Inhibitors; D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; D013565:Sympatholytics; D027981:Symporters; D019797:3-Iodobenzylguanidine; D003891:Desipramine; D009638:Norepinephrine