K(ATP) channels mediate the beneficial effects of chronic ethanol ingestion.
Chronic ingestion of low doses of ethanol protects the myocardium from ischemic injury by activating adenosine receptors and protein kinase C. We tested the hypothesis that ATP-dependent potassium (K(ATP)) channels mediate these beneficial effects. Dogs were fed with ethanol (1.5 g/kg) or water mixed with dry food twice per day for 12 wk. After they were acutely instrumented for measurement of hemodynamics, dogs received saline (vehicle) or glyburide (0.1 mg/kg iv) and were subjected to 60 min of coronary artery occlusion followed by 3 h of reperfusion. Infarct size (through triphenyltetrazolium chloride staining) was significantly (P < 0.05) reduced to 14 +/- 1% of the left ventricular area at risk in ethanol-pretreated dogs compared with controls (25 +/- 2%). Glyburide alone did not affect infarct size (25 +/- 3%) but abolished the protective effects of ethanol pretreatment (28 +/- 3%). No differences in hemodynamics or coronary collateral blood flow (through radioactive microspheres) were observed among groups. The results indicate that K(ATP) channels mediate the protective effects of chronic consumption of ethanol.
Pagel
P S
PS
Departments of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA. pspagel@mcw.edu
Toller
W G
WG
Gross
E R
ER
Gare
M
M
Kersten
J R
JR
Warltier
D C
DC
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004334:Drug Administration Schedule; D000431:Ethanol / Q000008:administration & dosage*; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015221:Potassium Channels / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism
D015221:Potassium Channels; D018047:Receptors, Purinergic P1; D000431:Ethanol; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D005905:Glyburide