The effect of gliclazide and glibenclamide on preconditioning of the human myocardium.
The cardioprotection of ischaemic preconditioning may be abolished in diabetic patients especially when some oral hypoglycaemics are used. The dose-response effect of gliclazide and glibenclamide on ischaemic preconditioning and the action of glibenclamide on signal transduction in human myocardium were investigated using right atrial appendages from cardiac surgery patients. Glibenclamide (0.1, 1, 3 and 10 microM) and gliclazide (1, 10, 30 and 100 microM) were added for 10 min prior to ischaemic preconditioning. The cardioprotection was abolished by glibenclamide at all concentrations and by gliclazide at supratherapeutic concentrations of 30 and 100 microM. Glibenclamide abolished the protective effect of mitoK(ATP) channel opening but not that of protein kinase C (PKC) or p38 mitogen activated protein kinase (p38MAPK) activation. In conclusion, glibenclamide and gliclazide differential effects may be a result of differential sensitivities. Glibenclamide does not block protection conferred by either PKC or p38MAPK activation. These findings may have clinical implications in ischaemic heart disease.
Loubani
Mahmoud
M
Department of Integrative Human Cardiovascular Physiology and Cardiac Surgery, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK.
Fowler
Alan
A
Standen
Nicholas B
NB
Galiñanes
Manuel
M
D000465:Algorithms; D020517:Atrial Appendage / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D003402:Creatine Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005907:Gliclazide / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D015221:Potassium Channels / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D007004:Hypoglycemic Agents; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D003402:Creatine Kinase; D005907:Gliclazide; D005905:Glyburide