Remote renal preconditioning-induced cardioprotection: a key role of hypoxia inducible factor-prolyl 4-hydroxylases |
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Authors: | Ravi Kant Vishal Diwan Amteshwar Singh Jaggi Nirmal Singh Dhandeep Singh |
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Institution: | (1) Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, Punjab, India |
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Abstract: | Remote preconditioning is a unique phenomenon in which brief episodes of ischemia and reperfusion to remote organ protect
the target organ against sustained ischemia–reperfusion (I/R)-induced injury. Protective effects of remote renal preconditioning
(RRPC) are well established in heart, but their mechanisms still remain to be elucidated. So, the present study was designed
to investigate the possible role of oxygen-sensing hypoxia inducible factor-prolyl 4-hydroxylases (HIF-P4Hs) in RRPC-induced
cardioprotection in rats. Remote renal preconditioning was performed by four episodes of 5 min renal artery occlusion and
reperfusion. Isolated rat hearts were perfused on Langendorff apparatus and were subjected to global ischemia for 30 min followed
by 120 min reperfusion. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were measured in coronary effluent
to assess the degree of myocardial injury. Extent of myocardial infarct size and coronary flow rate was also measured. Ethyl
3,4-dihydroxybenzoate (EDHB) and α-ketoglutarate (α-KG) were employed as HIF-P4Hs inhibitor and activator, respectively. Diethyldithiocarbamic
acid (DDCA) was employed as NFkB inhibitor. Remote renal preconditioning prevented I/R-induced myocardial injury and produced
cardioprotective effects. Pharmacological preconditioning with EDHB (100 mg kg−1 i.p.) mimicked the cardioprotective effects of RRPC. However, α-KG (200 mg kg−1 i.p.) and DDCA (150 mg kg−1 i.p.) abolished cardioprotective effects of RRPC and EDHB. So, it may be concluded that inhibition of HIF-P4H has a key role
in RRPC-induced cardioprotection. Further, remote preconditioning-induced HIF-P4H inhibition may have triggered a transduction
pathway involving activation of NFkB. |
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Keywords: | Prolyl 4-hydroxylases Remote renal preconditioning NFkB Cardioprotection |
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