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Role of inducible nitric oxide synthase in myocardial ischemia-reperfusion injury in sleep-deprived rats

  • Sleep Breathing Physiology and Disorders • Original Article
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Abstract

Introduction

REM sleep deprivation (SD) decreases tolerance of the rat heart to ischemia-reperfusion (IR) injury; the underlying mechanisms, however, are unknown. This study aimed at determining whether changes in iNOS, Bax, and Bcl-2 gene expression are involved in this detrimental effect.

Method

SD was induced by flowerpot technique for a period of 4 days. This method is simple and able to induce sleep fragmentation which occurs as one of the sleep disorder symptoms in clinical conditions. The hearts of control and SD rats were perfused in Langendorff apparatus and subjected to 30 min ischemia, followed by 90 min reperfusion. The hemodynamic parameters (left ventricular developed pressure (LVDP), and ± dp/dt), NOx (nitrite + nitrate) level, infarct size, and mRNA expression of iNOS, Bax, and Bcl-2 were measured after IR.

Results

SD rats had lower recovery of post-ischemic LVDP (32.8 ± 2.5 vs. 51.5 ± 2.1 mmHg; P < 0.05), + dp/dt (1555 ± 66 vs. 1119.5 ± 87 mmHg/s; P < 0.05) and − dp/dt (1437 ± 65 vs. 888 ± 162 mmHg/s; P < 0.05). SD rats also had higher NOx levels (41.4 ± 3.1 vs. 22.4 ± 3.6 μmol/L; P < 0.05) and infarct size (64.3 ± 2.3 vs. 38.3 ± 1.6%; P < 0.05) after IR, which along with LVDP, ± dp/dt restored to near normal status in the presence of aminoguanidine, a selective iNOS inhibitor. Following IR, expression of iNOS and Bax increased and Bcl-2 decreased (502, 372, and 54%, respectively) in SD rats; whereas in the presence of aminoguanidine, expression of iNOS and Bax significantly decreased and Bcl-2 increased (165, 168, and 19%, respectively).

Conclusion

Higher expression of iNOS and subsequent increase in apoptosis in the hearts after IR may contribute to less tolerance to myocardial IR injury in SD rats.

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Authors and Affiliations

  1. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sajad Jeddi & Asghar Ghasemi

  2. Aerospace Medicine Research Center, Medical Faculty of Aerospace and Subaquatic Medicine, AJA Medical Sciences University, Tehran, Iran

    Alireza Asgari & Amir Nezami-Asl

Authors
  1. Sajad Jeddi
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  2. Asghar Ghasemi
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  3. Alireza Asgari
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  4. Amir Nezami-Asl
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Corresponding author

Correspondence to Amir Nezami-Asl.

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Ethical approval

This study was approved by the local ethics committee of the Research Institute for Educational Sciences; all procedures were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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Jeddi, S., Ghasemi, A., Asgari, A. et al. Role of inducible nitric oxide synthase in myocardial ischemia-reperfusion injury in sleep-deprived rats. Sleep Breath 22, 353–359 (2018). https://doi.org/10.1007/s11325-017-1573-7

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  • DOI: https://doi.org/10.1007/s11325-017-1573-7

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