Effects of glibenclamide, glimepiride, and gliclazide on ischemic preconditioning in rat heart.
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.
Wu
Guo-ting
GT
Department of Endocrine and Metabolism, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072. wgt1212@hotmail.com
Wang
Lin
L
Li
Jun
J
Zhu
Wei-zhong
WZ
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*
D013453:Sulfonylurea Compounds; C057619:glimepiride; D005907:Gliclazide; D005905:Glyburide