Genistein, an inhibitor of tyrosine kinase, prevents the antiarrhythmic effects of preconditioning.
The possible involvement of tyrosine kinase in the signal transduction processes associated with the antiarrhythmic effects of ischaemic preconditioning was assessed by the administration, prior to the preconditioning stimulus, of the tyrosine kinase inhibitor genistein (5 mg/kg i.v.) to pentobarbitone anaesthetised male rats. The hearts were then removed, perfused by the Langendorff technique and preconditioned by a single brief (3 min) coronary artery occlusion prior to the 30 min test ischaemic insult. Preconditioning reduced ventricular arrhythmias during occlusion (e.g., premature ventricular beats from 333 +/- 60 in controls to 52 +/- 5 in preconditioned hearts; P < 0.05) but this protective effect was not observed in the hearts of rats given genistein (272 +/- 37 premature beats). A similar abolition of the protective effects of preconditioning could be demonstrated in hearts perfused in vitro with genistein (100 microM). This suggests the involvement of tyrosine kinase activation in this powerful form of endogenous cardioprotection.
Fatehi-Hassanabad
Z
Z
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK.
Parratt
J R
JR
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D017180:Tachycardia, Ventricular / Q000209:etiology
D004791:Enzyme Inhibitors; D019833:Genistein; D011505:Protein-Tyrosine Kinases