title: Resistance to store depletion-induced endothelial injury in rat lung after chronic heart failure.
abstract: BACKGROUND
  In chronic heart failure, the lung endothelial permeability response to angiotensin II or thapsigargin-induced store depletion is ablated, although the mechanisms are not understood.
  
  
  OBJECTIVE
  To determine whether the ablated permeability response to store depletion during heart failure was due to impaired expression of store operated Ca2+ channels in lung endothelium.
  
  
  METHODS
  Heart failure was induced by aortocaval fistula in rats. Permeability was measured in isolated lungs using the filtration coefficient and a low Ca2+/Ca2+ add-back strategy to identify the component of the permeability response dependent on Ca2+ entry.
  
  
  RESULTS
  In fistulas, right ventricular mass and left ventricular end diastolic pressure were increased and left ventricular shortening fraction decreased compared with shams. Thapsigargin-induced store depletion increased lung endothelial permeability in shams, but not in fistulas. Permeability increased in both groups after the Ca2+ ionophore A23187 or 14,15-epoxyeicosatrienoic acid, independent of store depletion. A diacylglycerol analog had no impact on permeability. Increased distance between the endoplasmic reticulum and the plasmalemmal membrane was ruled out as a mechanism for the loss of the permeability response to store depletion. Endothelial expression of the endoplasmic reticulum Ca2+ ATPase was not altered in fistulas compared with shams, whereas the store-operated canonical transient receptor potential channels 1, 3, and 4 were downregulated in extraalveolar vessel endothelium.
  
  
  CONCLUSIONS
  We conclude that the adaptive mechanism limiting store depletion-induced endothelial lung injury in the aortocaval model of heart failure involves downregulation of store-operated Ca2+ channels.
authors.affiliation: Department of Physiology, MSB 3074, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Diego F
authors.initials: DF
authors.lastname: Alvarez
authors.forename: Judy A
authors.initials: JA
authors.lastname: King
authors.forename: Mary I
authors.initials: MI
authors.lastname: Townsley
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004195:Disease Models, Animal; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006333:Heart Failure / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019284:Thapsigargin / Q000494:pharmacology*; D046509:Tissue Culture Techniques; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007476:Ionophores; D014665:Vasodilator Agents; D000001:Calcimycin; D019284:Thapsigargin; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D015126:8,11,14-Eicosatrienoic Acid