title: Role of atrial natriuretic peptide in ischemic preconditioning-induced cardioprotection in the diabetic rat heart.
abstract: BACKGROUND
  It has been noted that nitric oxide (NO) is involved in the ischemic preconditioning (IPC)-mediated cardioprotection. Diabetes is a downregulator of atrial natriuretic peptide (ANP), resulting in low expression of endothelial nitric oxide synthase (eNOS) by which NO level get reduced. The purpose of the present study was to investigate the role of ANP in attenuated cardioprotective effect of IPC in the diabetic rat heart.
  
  
  METHODS
  The heart was isolated from the diabetic rat and mounted on Langendorff's apparatus, subjected to 30-min ischemia and 120-min reperfusion. IPC was mediated by four cycles of 5-min ischemia and 5-min reperfusion. The infarct size was estimated using triphenyltetrazolium chloride stain, and coronary effluent was analyzed for lactate dehydrogenase and creatinine kinase-MB release to assess the degree of myocardial injury. The cardiac release of NO was estimated indirectly by measuring the release of nitrite in coronary effluent.
  
  
  RESULTS
  IPC-mediated cardioprotection was significantly attenuated in the diabetic rat as compared with the normal rat. Perfusion of ANP (0.1 μM/L) in the diabetic rat heart significantly restored the attenuated cardioprotective effect of IPC and also increased the release of NO. However, this observed cardioprotection was significantly attenuated by perfusion of N-nitro L-arginine methyl ester, an eNOS inhibitor (100 μM/L) noted in terms of increase in myocardial infarct size, release of lactate dehydrogenase and creatinine kinase-MB, and also decreases in release of NO.
  
  
  CONCLUSIONS
  Thus, it is suggested that ANP restores the attenuated cardioprotective effect in the diabetic heart which may be due to increase in the expression of eNOS and subsequent increase in the activity of NO.
authors.affiliation: Institute of Pharmaceutical Research, GLA University, Mathura, U.P, India. Electronic address: charankaali555@gmail.com.
authors.forename: Kali
authors.initials: K
authors.lastname: Charan
authors.affiliation: Institute of Pharmaceutical Research, GLA University, Mathura, U.P, India.
authors.forename: Ahsas
authors.initials: A
authors.lastname: Goyal
authors.affiliation: Institute of Pharmaceutical Research, GLA University, Mathura, U.P, India.
authors.forename: Jeetendra Kumar
authors.initials: JK
authors.lastname: Gupta
authors.affiliation: All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Harlokesh Narayan
authors.initials: HN
authors.lastname: Yadav
mesh_terms: D000496:Alloxan; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use*; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009573:Nitrites / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D009573:Nitrites; D000496:Alloxan; D009320:Atrial Natriuretic Factor; D007770:L-Lactate Dehydrogenase
keywords: Atrial natriuretic peptide; Diabetes; Ischemic preconditioning; Nitric oxide