Endothelin-1 and myocardial preconditioning.
This study attempted to define the role of endothelin (ET) in preconditioning. We previously showed that ET Is produced during myocardial ischemia and reperfusion. Because both preconditioning and ET act through protein kinase C, ET could play a role in preconditioning. Dogs were randomized to three groups subjected to 40 minutes of ischemia, with (groups A and B) or without (group C) preconditioning, followed by 4 hours of reperfusion. Groups A and C received saline infusions; group B received continuous infusions of the ETA-selective antagonist FR139317. Both preconditioned groups had smaller infarct sizes (group A, 7.9% +/- 2.5%; group B, 8.4% +/- 2.6%) than the nonpreconditioned group (group C, 16.2% +/- 3.3%). Administration of the ETA antagonist FR139317 did not alter infarct size. This study demonstrated that ETA-receptor blockade did not alter infarct size in preconditioned animals and suggests that endothelin does not play a significant role in this process.
Erikson
J M
JM
Cardiology Section, Veterans Affairs Medical Center, Dallas, Texas.
Velasco
C E
CE
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D007262:Infusions, Intravenous; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D015425:Myocardial Reperfusion; D010865:Pilot Projects; D011493:Protein Kinase C / Q000502:physiology; D011897:Random Allocation; D017466:Receptors, Endothelin / Q000187:drug effects; D012965:Sodium Chloride; D017180:Tachycardia, Ventricular / Q000209:etiology; D014693:Ventricular Fibrillation / Q000209:etiology
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D017466:Receptors, Endothelin; C079574:FR 139317; D012965:Sodium Chloride; D011493:Protein Kinase C