title: Oxidative stress increases pulmonary vascular permeability in diabetic rats through activation of transient receptor potential melastatin 2 channels.
abstract: OBJECTIVE
  In vitro superoxide activates pulmonary endothelial TRPM2 channels and increases Kf . We hypothesized that pulmonary capillary Kf is increased in a model of type I diabetes due to elevated vascular superoxide and resultant TRPM2 channel activation.
  
  
  METHODS
  Type I diabetes was induced in Zucker rats using STZ. Half of the STZ animals were treated with apocynin, a NOX inhibitor. After four weeks, lung Kf was measured in the isolated lung in the presence or absence of TRPM2 inhibitors (2-APB and FA). In an additional set of experiments, Kf was measured in nondiabetic Zucker rats after applying the superoxide donor (PMS).
  
  
  RESULTS
  As compared to control rats, hyperglycemic rats exhibited increased vascular superoxide and Kf , along with decreased lung vascular TRPM2-L expression. Apocynin treatment reduced superoxide and Kf in hyperglycemic rats with no effect in control rats. TRPM2 channel inhibition decreased Kf in hyperglycemic rats with no effect in control rats. PMS increased the lung Kf in control rats, with TRPM2 inhibition attenuating this response.
  
  
  CONCLUSIONS
  Diabetic rats exhibit a TRPM2-mediated increase in lung Kf , which is associated with increased TRPM2 activation and increased vascular superoxide levels.
authors: Department of Physiology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors: Silu
authors: S
authors: Lu
authors: Lusha
authors: L
authors: Xiang
authors: John S
authors: JS
authors: Clemmer
authors: Peter N
authors: PN
authors: Mittwede
authors: Robert L
authors: RL
authors: Hester
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001896:Boron Compounds / Q000494:pharmacology; D002199:Capillary Permeability; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001896:Boron Compounds; D050053:TRPM Cation Channels; C557080:Trpm2 protein, rat; C056165:acetovanillone; C109986:2-aminoethoxydiphenyl borate; D011188:Potassium
keywords: TRPM2; hyperglycemia; lung permeability; superoxide