Possible role of adrenergic component and cardiac mast cell degranulation in preconditioning-induced cardioprotection.
The present study was designed to investigate the role of adrenergic component and cardiac mast cell degranulation in the cardioprotective effect of ischaemic preconditioning. Isolated rat hearts were subjected to 30 min of global ischaemia followed by 30 min of reperfusion. Ischaemic/norepinephrine (100 microm) preconditioning markedly reduced ischaemia-reperfusion-induced release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent and the incidence of ventricular premature beats (VPBs) and ventricular tachycardia/fibrillation (VT/VF) during the reperfusion phase. Moreover, ischaemic/norepinephrine preconditioning significantly reduced ischaemia-reperfusion-induced release of mast cell peroxidase (MPO), a marker of mast cell degranulation. Prazosin (0.1 microm), a alpha(1)adrenoceptor blocker, administered during ischaemic/norepinephrine preconditioning attenuated the cardioprotective and antiarrhythmic effect of ischaemic/norepinephrine preconditioning. MPO release increased immediately after ischaemic/norepinephrine preconditioning and the release was found to be inhibited in hearts subjected to ischaemic/norepinephrine preconditioning in the presence of prazosin. However, prazosin (0.1 microm) treatment per se produced cardioprotective and antiarrhythmic effects and reduced ischaemia-reperfusion-induced MPO release. These findings tentatively suggest that ischaemic preconditioning produced cardioprotective and antiarrhythmic effect by activating alpha(1)adrenoceptors and consequent degranulation of cardiac mast cells. Prazosin administered during ischaemic preconditioning abolished its ameliorative effect.
Parikh
V
V
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
Singh
M
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D015550:Cell Degranulation / Q000187:drug effects*; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000494:pharmacology; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011941:Receptors, Adrenergic; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D003402:Creatine Kinase; D009638:Norepinephrine; D011224:Prazosin