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

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.

Melatonin Reduces Androgen Production and Upregulates Heme Oxygenase-1 Expression in Granulosa Cells from PCOS Patients with Hypoestrogenia and Hyperandrogenia

“…Levels of NO in FF were found to affect the development and fertilization of oocytes [43]. Levels of iNOS protein in the hearts of dihydroxytestosterone-treated rats were significantly elevated [44]. In this study, we observed higher lipid peroxidation in the FF of PCOS patients.…”

Cardiovascular Properties of the Androgen‐Induced PCOS Model in Rats: The Role of Oxidative Stress

“…In this sense, the androgen-induced PCOS model could be appropriate to examine both ovarian morphology and metabolic aspects of PCOS. Regarding the PCOS rat model and CV features, it is known that rats with PCOS showed increased sympathetic activity and HT [12], as well as impaired NO synthase and Na/K-ATP-ase activity in the heart tissue [13].…”

“…On the contrary, prooxidative effects of testosterone and its derivatives on CV [17], endocrine [18], and behavioral [19,20] properties were proven in our previous papers, dealing with the administration of supraphysiological doses in male rats. Investigations with similar protocols in female rodents have not been represented in literature so far, except androgen administration to female rats to mimic PCOS characteristics [13]. The data concerning PCOS models demonstrated increased oxidative stress with impairment of antioxidant protection in different tissues, such as liver, muscle, and periovarial fat tissue [21].…”

Oxidative stress level among females with Type 2 Diabetes Mellitus with & without Polycystic Ovarian Syndrome.

“…However, these are the vital enzyme acting as an antitoxin against anion of super oxide16. Similarly, in a few studies, it was also found that elevation of oxidative pressure was observed even in obese females with PCOs 17 . Literature in the past suggests that the concentration of extracellular SOD increases after a vascular injury that significantly leads to vascular endothelium tissue damage 18 .…”