title: Preconditioning offers cardioprotection in hyperlipidemic rat hearts: possible role of Dopamine (D2) signaling.
abstract: BACKGROUND
  Ischemic preconditioning (IPC) induced cardioprotection has been reported to be blunted in hyperlipidemic subjects. Dopamine, via its D2 receptor signaling, appears to mimic the signaling cascade involved in myocardial preconditioning and is also involved in the inhibition of hyperlipidemia induced mediators. The present study was designed to investigate the possible involvement of D2 receptors in IPC and to see whether dopamine preconditioning can offer cardioprotection in hyperlipidemic rat hearts.
  
  
  METHODS
  Wistar albino rats were divided into 8 groups and fed on normal or high fat diet for 4 weeks. Hyperlipidemia was confirmed after 4 weeks by serum lipid estimations. Isolated perfused hearts were subjected to ischemic preconditioning or dopamine induced pharmacological preconditioning followed by 30-min ischemic insult and 60-min reperfusion. Clozapine was administered as D2 antagonist. Coronary perfusate (basal and post-ischemic) was collected for the estimations of LDH (Lactate dehydrogenase) and CKMB (Creatine kinase MB). Hearts were then removed and frozen for infarct size measurement.
  
  
  RESULTS
  A significant increase body weight, serum lipids except HDL was noted in high fat diet fed rats, as compared to normal rats. The level of LDH, CKMB in coronary effluent and infarct size were found to be decreased in preconditioned normal hearts, as compared to hearts treated with ischemia reperfusion. This effect was found to be blunted in hyperlipidemic animals. Dopamine (10 μM) alone and in combination with ischemic preconditioning significantly reduced the levels of LDH, CKMB and infarct size in hyperlipidemic hearts, as compared to preconditioned and non-preconditioned hyperlipidemic hearts. This effect was abolished significantly by Clozapine (D2 antagonist).
  
  
  CONCLUSIONS
  The present study reveals possible involvement of D2 receptors in ischemic preconditioning and suggests that dopamine preconditioning may offer significant cardioprotection in hyperlipidemic rat hearts.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Shoolini University, Solan, HP, 173212, India.
authors.forename: Varun
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Shoolini University, Solan, HP, 173212, India. rohit_pharm@yahoo.co.in.
authors.forename: Rohit
authors.initials: R
authors.lastname: Goyal
authors.affiliation: Department of Pharmacology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Pyare Lal
authors.initials: PL
authors.lastname: Sharma
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006949:Hyperlipidemias / Q000097:blood / Q000517:prevention & control*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2