Role of Heme-Oxygenase- 1 in Attenuated Cardioprotective Effect of Ischemic Preconditioning in Hyperlipidemic Myocardium

1
Atinderpal Kaur
Atinderpal Kaur
2
Tapan Behl
Tapan Behl
3
H. N. Yadav
H. N. Yadav
4
PL Sharma
PL Sharma
1 I.S.F College of Pharmacy
2 Delhi University

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Role of Heme-Oxygenase- 1 in Attenuated Cardioprotective Effect of Ischemic  Preconditioning in Hyperlipidemic Myocardium Banner
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Nitric Oxide (NO) is responsible for cardioprotective effect of ischemic preconditioning (IPC). Heme Oxygenase-1 (HO-1) facilitates release of NO by disrupting caveolin-eNOS complex. Both, the expression/activity of HO-1 and the IPC mediated cardioprotection are decreased significantly in hyperlipidemia. In this study the role of HO-1 in attenuation of IPC-induced cardioprotective effect in hyperlipidemic rat was investigated. Hyperlipidemia was induced by feeding high fat diet to Wistar rats. Isolated Langendorff heart preparation model was used. Cardioprotective effect was assessed by myocardial infarct size measurement and release of Lactate Dehydrogenase (LDH), Creatine Kinase (CK-MB) in coronary effluent. Nitrite estimation was done to indirectly infer the level of cardiac NO production. In hyperlipidemic rat, IPC-induced cardioprotection and release of NO were significantly decreased. Perfusion with sodium nitrite (NO precursor) and pre-treatment with daidzein (DDZ) (caveolin inhibitor) and hemin (HO-1 inducer), alone or in combination significantly restored the attenuated cardioprotective effect of IPC in hyperlipidemic rats. Administration of zinc protoporphyrin (ZnPP), HO-1 inhibitor, significantly abolished the observed cardioprotection in hemin pre-treated hyperlipidemic rat. The significant restoration of the attenuated cardioprotective effect of IPC following induction of HO-1 by hemin in hyperlipidemia was observed. The results indicated that attenuation of IPC-induced cardioprotective effect may be due to the decrease in HO-1 induced NO release in hyperlipidemic rat heart.

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Funding

No external funding was declared for this work.

Conflict of Interest

The authors declare no conflict of interest.

Ethical Approval

No ethics committee approval was required for this article type.

Data Availability

Not applicable for this article.

Atinderpal Kaur. 2017. \u201cRole of Heme-Oxygenase- 1 in Attenuated Cardioprotective Effect of Ischemic Preconditioning in Hyperlipidemic Myocardium\u201d. Global Journal of Medical Research - B: Pharma, Drug Discovery, Toxicology & Medicine GJMR-B Volume 17 (GJMR Volume 17 Issue B3): .

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Crossref Journal DOI 10.17406/gjmra

Print ISSN 0975-5888

e-ISSN 2249-4618

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November 3, 2017

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Nitric Oxide (NO) is responsible for cardioprotective effect of ischemic preconditioning (IPC). Heme Oxygenase-1 (HO-1) facilitates release of NO by disrupting caveolin-eNOS complex. Both, the expression/activity of HO-1 and the IPC mediated cardioprotection are decreased significantly in hyperlipidemia. In this study the role of HO-1 in attenuation of IPC-induced cardioprotective effect in hyperlipidemic rat was investigated. Hyperlipidemia was induced by feeding high fat diet to Wistar rats. Isolated Langendorff heart preparation model was used. Cardioprotective effect was assessed by myocardial infarct size measurement and release of Lactate Dehydrogenase (LDH), Creatine Kinase (CK-MB) in coronary effluent. Nitrite estimation was done to indirectly infer the level of cardiac NO production. In hyperlipidemic rat, IPC-induced cardioprotection and release of NO were significantly decreased. Perfusion with sodium nitrite (NO precursor) and pre-treatment with daidzein (DDZ) (caveolin inhibitor) and hemin (HO-1 inducer), alone or in combination significantly restored the attenuated cardioprotective effect of IPC in hyperlipidemic rats. Administration of zinc protoporphyrin (ZnPP), HO-1 inhibitor, significantly abolished the observed cardioprotection in hemin pre-treated hyperlipidemic rat. The significant restoration of the attenuated cardioprotective effect of IPC following induction of HO-1 by hemin in hyperlipidemia was observed. The results indicated that attenuation of IPC-induced cardioprotective effect may be due to the decrease in HO-1 induced NO release in hyperlipidemic rat heart.

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Role of Heme-Oxygenase- 1 in Attenuated Cardioprotective Effect of Ischemic Preconditioning in Hyperlipidemic Myocardium

Atinderpal Kaur
Atinderpal Kaur I.S.F College of Pharmacy
Tapan Behl
Tapan Behl Delhi University
H. N. Yadav
H. N. Yadav
PL Sharma
PL Sharma

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