Back to Search
Start Over
The role of arginase and rho kinase in cardioprotection from remote ischemic perconditioning in non-diabetic and diabetic rat in vivo
- Source :
- PLoS ONE, PLoS ONE, Vol 9, Iss 8, p e104731 (2014)
- Publication Year :
- 2014
-
Abstract
- BackgroundPharmacological inhibition of arginase and remote ischemic perconditioning (RIPerc) are known to protect the heart against ischemia/reperfusion (IR) injury.PurposeThe objective of this study was to investigate whether (1) peroxynitrite-mediated RhoA/Rho associated kinase (ROCK) signaling pathway contributes to arginase upregulation following myocardial IR; (2) the inhibition of this pathway is involved as a cardioprotective mechanism of remote ischemic perconditioning and (3) the influence of diabetes on these mechanisms.MethodsAnesthetized rats were subjected to 30 min left coronary artery ligation followed by 2 h reperfusion and included in two protocols. In protocol 1 rats were randomized to 1) control IR, 2) RIPerc induced by bilateral femoral artery occlusion for 15 min during myocardial ischemia, 3) RIPerc and administration of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA), 4) administration of the ROCK inhibitor hydroxyfasudil or 5) the peroxynitrite decomposition catalyst FeTPPS. In protocol 2 non-diabetic and type 1 diabetic rats were randomosed to IR or RIPerc as described above.ResultsInfarct size was significantly reduced in rats treated with FeTPPS, hydroxyfasudil and RIPerc compared to controls (PConclusionArginase is activated by peroxynitrite/ROCK signaling cascade in myocardial IR. RIPerc protects against IR injury via a mechanism involving inhibition of this pathway and enhanced eNOS activation. The beneficial effect and associated molecular changes of RIPerc is abolished in type 1 diabetes.
- Subjects :
- Male
Critical Care and Emergency Medicine
Science
Cardiology
Myocardial Reperfusion Injury
Pharmacology
Research and Analysis Methods
Vascular Medicine
Diabetes Mellitus, Experimental
Rats, Sprague-Dawley
chemistry.chemical_compound
Ischemia
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Peroxynitrous Acid
Medicine and Health Sciences
Medicine
Animals
Enzyme Inhibitors
Ischemic Preconditioning
Rho-associated protein kinase
Trauma Medicine
Cardioprotection
rho-Associated Kinases
Multidisciplinary
omega-N-Methylarginine
biology
Arginase
business.industry
Rats
Nitric oxide synthase
Peroxynitrous acid
Biochemistry
chemistry
Reperfusion Injury
biology.protein
Animal Studies
Ischemic preconditioning
Omega-N-Methylarginine
business
Peroxynitrite
Signal Transduction
Research Article
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....3638f8c513a49bd19c8b0d75d2c07883