title: L-arginine administration recovers sarcoplasmic reticulum function in ischemic reperfused hearts by preventing calpain activation.
abstract: OBJECTIVE
  Earlier studies have shown that impaired cardiac contractility in ischemia reperfusion (IR) is associated with alterations in sarcoplasmic reticulum (SR) function. Impaired release of nitric oxide (NO) has been reported during IR, while administration of NO donors, such as L-arginine (LA), has been shown to improve cardiac performance in IR hearts. We therefore investigated the mechanisms underlying the recovery of contractile function in IR hearts treated with LA.
  
  
  METHODS
  Isolated rat hearts subjected to 30 min of global ischemia were reperfused for 60 min. The effects of LA on cardiac performance, SR function and its regulation were examined.
  
  
  RESULTS
  IR-induced impairment in cardiac performance was associated with a reduction in SR function and its regulation. IR caused an increase in calpain activity and a decrease in the sarcolemmal and SR nitric oxide synthase (NOS) isoform protein content as well as cytosolic NO levels. Administration of LA prevented contractile dysfunction in IR hearts, which was associated with a recovery of SR function and SR regulation by protein phosphorylation. This was consistent with a recovery in protein levels of major SR Ca2+-cycling and Ca2+-regulatory proteins. LA treatment attenuated an increase in calpain activity, possibly by nitrosylation of calpain, and increased cytosolic NO levels and SR NOS protein content in IR hearts.
  
  
  CONCLUSIONS
  These results suggest that LA administration improved cardiac contractility by preventing alterations in SR Ca2+ handling and calpain activation in IR hearts.
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, Manitoba, Canada R2H 2A6.
authors.forename: Punam K
authors.initials: PK
authors.lastname: Chohan
authors.forename: Raja B
authors.initials: RB
authors.lastname: Singh
authors.forename: Naranjan S
authors.initials: NS
authors.lastname: Dhalla
authors.forename: Thomas
authors.initials: T
authors.lastname: Netticadan
mesh_terms: D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001120:Arginine; D019001:Nitric Oxide Synthase; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002154:Calpain; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester