Possible role of nitric oxide and mast cells in endotoxin-induced cardioprotection.
The present study is designed to investigate the role of nitric oxide (NO) and cardiac mast cells in the cardioprotective effect of endotoxin in isolated rat heart subjected to 30 min of global ischaemia and 30 min of reperfusion. Endotoxin (2.5 mg kg(-1); i.p.) was administered 8 h before subjecting the heart to global ischaemia. Endotoxin pretreatment markedly reduced the release of lactate dehydrogenase (LDH) and creatine kinase (CK), markers of cardiac injury, in coronary effluent and the percentage incidence of ventricular premature beats (VPBs) and ventricular tachycardia/fibrillation (VT/VF) during the reperfusion phase. Endotoxin pretreatment significantly increased the release of nitrite prior to and after global ischaemia. On the other hand, endotoxin pretreatment decreased the release of mast cell peroxidase (MPO) during the reperfusion phase. The cardioprotective and antiarrhythmic effect of endotoxin pretreatment was abolished by dexamethasone (3 mg kg(-1); i.p.) or l -canavanine (20 mg kg(-1); i.p.) given 1 h before the administration of endotoxin. It is proposed that the cardioprotective and antiarrhythmic effect of the endotoxin may be ascribed to the induction of nitric oxide synthase (NOS) and subsequent increase in the release of NO. NO may stabilize cardiac mast cells and consequently decrease the release of cytotoxic mediators from these cells. Prevention of degranulation of cardiac mast cells may be responsible for the cardioprotective and antiarrhythmic effects of the endotoxin.
Parikh
V
V
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, India. vinaykparikh@usa.net
Singh
M
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002172:Canavanine / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D015550:Cell Degranulation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004334:Drug Administration Schedule; D004731:Endotoxins / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D066298:In Vitro Techniques; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000889:Anti-Arrhythmia Agents; D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D009573:Nitrites; D009569:Nitric Oxide; D002172:Canavanine; D003907:Dexamethasone; D010544:Peroxidases