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Nitric oxide synthase inhibition abrogates hydrogen sulfide-induced cardioprotection in mice

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Abstract

The cardioprotective property of hydrogen sulfide (H2S) is recently reported. However, cellular signaling cascades mediated by H2S are largely unclear. This study was undertaken to explore the molecular mechanism of H2S-induced cardioprotection in mouse heart by utilizing in vivo model of cardiac injury. We report here that intraperitoneal administration of sodium hydrogen sulfide (NaHS, 50 μmol kg−1 day−1 for 2 days), a H2S donor, significantly (P ≤ 0.05) increased nitric oxide levels in serum as well as myocardium without any sign of myocardial injury. Typical characteristics of myocardial injury induced by isoproterenol (ISO) administration was significantly (P ≤ 0.05) abrogated by NaHS administration as evidenced from reduction in elevated thiobarbituric acid reactive substances (TBARS) and normalization of glutathione (GSH), glutathione peroxidase, superoxide dismutase (SOD), and catalase activity. Further, decrease in TNF-α expression and improvement in myocardial architecture was also observed. However, co-administration of N-nitro-l-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor, and Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor along with NaHS and ISO abrogated the beneficial effect of H2S differentially. Inhibition of NOS significantly (P ≤ 0.05) increased serum creatine kinase, lactate dehydrogenase, serum glutamic oxaloacetic transaminase activity and myocardial TBARS, along with significant (P ≤ 0.05) reduction of myocardial GSH, SOD, and catalase. This was followed by increase in TNF-α expression and histopathological changes. Our results revealed that H2S provides myocardial protection through interaction with NOS and COX-2 pathway and inhibition of NOS completely abrogates the hydrogen sulfide-induced cardioprotection in mice.

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Acknowledgments

Financial support was provided by Ramalingaswami Fellowship fund (SKB) from Department of Biotechnology (DBT), Senior Research Fellowship (AK) from Council of Scientific and Industrial Research (CSIR), Government of India and IICT institute fund. We wish to thank Dr J S Yadav, Director, IICT, Hyderabad for providing all kind of support for this study and gratefully acknowledge Dr Rajkumar Banerjee for his suggestions and critical review of the manuscript.

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Authors and Affiliations

  1. Division of Pharmacology and Chemical Biology, Indian Institute of Chemical Technology, Hyderabad, India

    Bhavesh Sojitra, Yogesh Bulani, Abhinav Kanwal, Prachi Gupta, Madhusudana Kuncha & Sanjay Kumar Banerjee

  2. Department of Pathology, National Institute of Nutrition, Hyderabad, India

    Uday Kumar Putcha

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  1. Bhavesh Sojitra
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  2. Yogesh Bulani
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  4. Abhinav Kanwal
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Correspondence to Sanjay Kumar Banerjee.

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Bhavesh Sojitra and Yogesh Bulani contributed equally to this study.

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Sojitra, B., Bulani, Y., Putcha, U.K. et al. Nitric oxide synthase inhibition abrogates hydrogen sulfide-induced cardioprotection in mice. Mol Cell Biochem 360, 61–69 (2012). https://doi.org/10.1007/s11010-011-1044-6

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