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Exp Clin Endocrinol Diabetes 2015; 123(05): 303-307
DOI: 10.1055/s-0035-1548929
Article
© Georg Thieme Verlag KG Stuttgart · New York

Cardiac Nitric Oxide Synthases and Na+/K+-ATPase in the Rat Model of Polycystic Ovary Syndrome Induced by Dihydrotestosterone

S. Tepavčević
1   Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
D. V. Milutinović
2   Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
,
D. Macut
3   Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia
,
J. Stanišić
1   Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
M. Nikolić
2   Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
,
I. Božić-Antić
3   Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia
,
S. Rodaljević
1   Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
J. Bjekić-Macut
4   CHC Bežanijska kosa, Belgrade, Serbia
,
G. Matić
2   Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
,
G. Korićanac
1   Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
› Author Affiliations
Further Information

Publication History

received 30 December 2014
first decision 20 March 2015

accepted 31 March 2015

Publication Date:
19 May 2015 (online)

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Abstract

Nitric oxide synthases (NOSs) and Na+/K+-ATPase are enzymes essential for regular functioning of the heart. Since both enzymes are under insulin and androgen regulation and since insulin action and androgen level were disturbed in polycystic ovary syndrome (PCOS), we hypothesized that cardiac nitric oxide (NO) production and sodium/potassium transport would be deteriorated in PCOS. To test our hypothesis we introduced animal model of PCOS based on dihydrotestosterone (DHT) treatment of female Wistar rats and analyzed protein expression, phosphorylation or subcellular localization of endothelial NOS (eNOS), inducible NOS (iNOS) and alpha subunits of Na+/K+-ATPase in the heart. Obtained results indicate that DHT treatment significantly decreased cardiac eNOS protein level and activating phosphorylation at serine 1 177, while inhibitory phosphorylation at threonine 495 was increased. In contrast to expression of eNOS, iNOS protein level in the heart of DHT-treated rats was significantly elevated. Furthermore, cardiac protein level of alpha 1 subunit of the ATPase, as well as its plasma membrane content, were decreased in rats with PCOS. In line with this, alpha 2 subunit protein level in fraction of plasma membranes was also significantly below control level. In conclusion, DHT treatment impaired effectiveness of NOSs and Na+/K+-ATPase in the female rat heart. Regarding the importance of NO production and sodium/potassium transport in the cardiac contraction and blood flow regulation, it implicates strong consequences of PCOS for heart functioning.

Key words

polycystic ovary syndrome - dihydrotestosterone - nitric oxide synthase - Na+/K+-ATPase - heart
 

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