Pertussis toxin abolishes the cardioprotective effect of ischemic preconditioning in intact rat heart.
It has been previously demonstrated that Gi/o proteins are involved in ischemic preconditioning (IPC) in rabbits and dogs; however, there has been controversy as to the role of Gi/o proteins in IPC in in vivo rat infarct models. Therefore, the role of G proteins in the cardioprotective effect of IPC in a rat infarct model was reevaluated. Cardioprotection as indicated by infarct size (IS) as a percentage of the area at risk (IS/AAR) was determined by triphenyltetrazolium stain. The control group, which was subjected to 30 min of occlusion (Occ) and 2 h of reperfusion (Rep), had an IS/AAR of 46 +/- 6%. A single 5-min Occ followed by 10 min of Rep (1x PC) as well as three 5-min Occ periods interspersed with 5 min of Rep (3x PC) markedly reduced IS/AAR (6 +/- 1 and 8 +/- 1%, respectively). Pretreatment with pertussis toxin (10 microg/kg ip) for 48 h before 1x PC or 3x PC completely abolished their cardioprotective effects (46 +/- 5 and 38 +/- 4%, respectively). Pertussis toxin had no effect on IS/AAR and did not inactivate Gi/o proteins as assessed by an in vitro ADP-ribosylation assay of heart homogenates. These results demonstrate that the cardioprotective effect of IPC is mediated by a small subpopulation of Gi/o proteins in the intact rat heart.
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
J E
JE
Schultz
A K
AK
Hsu
J T
JT
Barbieri
P L
PL
Li
G J
GJ
Gross
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D004285:Dogs; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009243:NAD / Q000378:metabolism; D037342:Pertussis Toxin; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010566:Virulence Factors, Bordetella; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000241:Adenosine; D000109:Acetylcholine