title: The role of Na+/H+ exchanger in Ca2+ overload and ischemic myocardial damage in hearts from type 2 diabetic db/db mice.
abstract: BACKGROUND
  A higher increase in intracellular Na(+) via Na(+)/H(+) exchanger (NHE) during ischemia has been reported in type 2 diabetic mouse hearts. We investigated the role of NHE in inducing changes in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) and alterations in ventricular function during ischemia-reperfusion in type 2 diabetic mouse hearts.
  
  
  METHODS
  Hearts from male type 2 diabetic db/db (12-15 weeks old) and age-matched control db/+ mice were subjected to Langendorff perfusion and loaded with 4 μM of the Ca(2+) indicator fura-2. The hearts were exposed to no-flow ischemia for 15 minutes and then reperfused. [Ca(2+)](i) was measured by monitoring fura-2 fluorescence at 500 nm (excitation wavelengths of 340 and 380 nm), while left ventricular (LV) pressure was simultaneously measured.
  
  
  RESULTS
  db/db hearts exhibited a lower recovery of LV developed pressure than db/+ hearts during reperfusion following ischemia. Diastolic [Ca(2+)](i) was increased to a greater level in diabetic hearts than in the control hearts during ischemia and reperfusion. Such an increase in cytoplasmic Ca(2+) overload during ischemia-reperfusion in diabetic hearts was markedly reduced in the presence of the NHE inhibitor cariporide. This was accompanied by a significantly improved recovery of ventricular function on reperfusion, as shown by a lower increase in diastolic pressure and increased recovery of developed pressure.
  
  
  CONCLUSIONS
  NHE plays a key role in enhancing cytoplasmic Ca(2+) overload during ischemia-reperfusion and severely impairing post-ischemic cardiac function in hearts from type 2 diabetic db/db mice.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan. anzawar@jikei.ac.jp
authors.forename: Ryuko
authors.initials: R
authors.lastname: Anzawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Seki
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Nagoshi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Taniguchi
authors.forename: Danielle
authors.initials: D
authors.lastname: Feuvray
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D002118:Calcium