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Effect of nitrate and l-arginine therapy on nitric oxide levels in serum, heart, and aorta of fetal hypothyroid rats

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Abstract

Reduced nitric oxide availability and a heterogeneous pattern of nitric oxide synthase activity in some tissues have been reported in hypothyroidism. This study aimed at determining the effects of oral nitrate and l-arginine administration on serum, heart, and aorta nitric oxide metabolite concentrations in fetal hypothyroid rats. In an experimental study, pregnant Wistar rats were administrated tap water or 0.02 % of 6-propyl-2-thiouracil in drinking water during pregnancy and their male pups were followed (n = 8/group). In adult progeny, serum, heart, and aorta nitric oxide metabolite concentrations were measured by the Griess method after 1-week administration of sodium nitrate (500 mg/L) or l-arginine (2 %) in drinking water. Serum thyroid hormone and thyroid-stimulating hormone levels were also measured. Compared to controls, fetal hypothyroid progeny had significantly lower nitric oxide metabolite concentrations in heart (0.32 ± 0.07 vs. 0.90 ± 0.14 nmol/mg protein, p = 0.004) and aorta (2.98±0.56 vs. 6.15±0.74 nmol/mg protein, p = 0.011) tissues. Nitrate therapy restored heart nitric oxide metabolite levels decreased by fetal hypothyroidism, while l-arginine administration further decreased aorta nitric oxide metabolite levels. Sodium nitrate increased and l-arginine decreased serum nitric oxide metabolite levels in both control and fetal hypothyroid animals. In conclusion, nitrate therapy restores decreased heart nitric oxide metabolite levels, whereas l-arginine decreases aorta nitric oxide metabolite levels even further in fetal hypothyroid rats, findings relevant to the cardiovascular consequences of congenital hypothyroidism in adulthood.

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Acknowledgments

This work was supported by grant no. 350 from the Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences. The authors wish to thank Dr. M. Tohidi for assisting in hormone assays and Ms N. Shiva for critical editing of English grammar and syntax of the manuscript.

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Authors and Affiliations

  1. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Parvaneh Street, Velenjak, P.O. Box: 19395-4763, Tehran, Iran

    Asghar Ghasemi & Saleh Zahediasl

  2. Biology Department, Islamic Azad University, Damghan Branch, Damghan, Iran

    Fatemeh Mehrazin

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  1. Asghar Ghasemi
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  2. Fatemeh Mehrazin
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Correspondence to Asghar Ghasemi.

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Ghasemi, A., Mehrazin, F. & Zahediasl, S. Effect of nitrate and l-arginine therapy on nitric oxide levels in serum, heart, and aorta of fetal hypothyroid rats. J Physiol Biochem 69, 751–759 (2013). https://doi.org/10.1007/s13105-013-0251-x

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  • DOI: https://doi.org/10.1007/s13105-013-0251-x

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