title: Effects of glibenclamide, glimepiride, and gliclazide on ischemic preconditioning in rat heart.
abstract: OBJECTIVE
  To compare the influence of different sulfonylureas on the myocardial protection effect of ischemic preconditioning (IPC) in isolated rat hearts, and ATP-sensitive potassium channel current (IK(ATP)) of rat ventricular myocytes.
  
  
  METHODS
  Isolated Langendorff perfused rat hearts were randomly assigned to five groups: (1) control group, (2) IPC group, (3) IPC + glibenclamide (GLB, 10 micromol/L) group, (4) IPC + glimepiride (GLM, 10 micromol/L) group, (5) IPC + gliclazide (GLC, 50 micromol/L) group. IPC was defined as 3 cycles of 5-minute zero-flow global ischemia followed by 5-minute reperfusion. The haemodynamic parameters and the infarct size of each isolated heart were recorded. And the sarcolemmal IK(ATP) of dissociated ventricular myocytes reperfused with 10 micromol/L GLB, 1 micromol/L GLM, and 1 micromol/L GLC was recorded with single-pipette whole-cell voltage clamp under simulated ischemic condition.
  
  
  RESULTS
  The infarct sizes of rat hearts in IPC (23.7% +/- 1.3%), IPC + GLM (24.6% +/- 1.0%), and IPC + GLC (33.1% +/- 1.3%) groups were all significantly smaller than that in control group (43.3% +/- 1.8%; P < 0.01, n = 6). The infarct size of rat hearts in IPC + GLB group (40.4% +/- 1.4%) was significantly larger than that in IPC group (P < 0.01, n=6). Under simulated ischemic condition, GLB (10 micromol/L) decreased IK(ATP) from 20.65 +/- 7.80 to 9.09 +/- 0.10 pA/pF (P < 0.01, n=6), GLM (1 micromol/L) did not significantly inhibit IK(ATP) (n=6), and GLC (1 micromol/L) decreased IK(ATP) from 16.73 +/- 0.97 to 11. 18 +/- 3.56 pA/pF (P < 0.05, n=6).
  
  
  CONCLUSIONS
  GLM has less effect on myocardial protection of IPC than GLB and GLC. Blockage of sarcolemmal ATP-sensitive potassium channels in myocardium might play an important role in diminishing IPC-induced protection of GLM, GLB, and GLC.
authors.affiliation: Department of Endocrine and Metabolism, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072. wgt1212@hotmail.com
authors.forename: Guo-ting
authors.initials: GT
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Wei-zhong
authors.initials: WZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D005907:Gliclazide / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D019194:Ischemic Preconditioning; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
chemical_list: D013453:Sulfonylurea Compounds; C057619:glimepiride; D005907:Gliclazide; D005905:Glyburide