Aortic Function and Ntrative Stress in a Rat Model of Polycystic Ovary Syndrome

Objective: Polycystic ovary syndrome (PCOS) represents the most prevalent endocrine disorder in women of fertile age; besides infertility, an elevated cardiovascular risk was described. Vitamin D hypovitaminosis affects about 80-90% of PCOS patients. Our team assessed aortic function and nitrative stress in a hyperandrogenic rat model and the effectiveness of Vitamin D substitution. Design and method: Female Wistar rats at the age of 3-4 weeks were randomly assigned into four groups. Eight rats received no treatment (controls, C), eight rats received weekly Vitamin D per os (140 IU/100 g body weight, group D), eight received cutaneous testosterone daily (3.3 mg/100 g, T) and eight received Vitamin D and testosterone (T+D). At the eighth week of the treatment, aortic rings were isolated for analysis: they were cut into 3-4 mm long segments for myography, other segments were formaldehyde fixed and paraffin embedded to assess, by immunohistochemical methods, nitrative stress markers (nitrotyrosine, NT) and DNA breaks signaled by nuclear poly(ADP-ribose) polymer (PAR) detection. Results: The weight gains of the two testosterone-treated groups were significantly higher between the 6-8 weeks compared to the other two groups, Vitamin D treatment did not influence body weight. Rats in the C and D groups had 3 or 4 estruses in the last 14 days. T rats had 1 or 2 estruses during the same period. T+D rats had 1-2 (N=3), or 3-4 (N=5) estruses. Aortic contraction, induced by the alpha1-adrenergic agonist phenylephrine, was significantly elevated in T and T+D animals in comparison to controls and Vitamin D treated rats. The endothelium-mediated aortic relaxation, as a response to acetyl-choline and insulin, was unaltered; however, estrogen-induced relaxation was significantly impaired in T and T+D groups. According to resorcin-fuchsin staining, no fibrotic alteration was detected. Nitrative stress and poly(ADP-ribosyl)ation were similar in all four groups. Conclusions: Eight weeks of testosterone administration caused increased weight gain and sex cycle lengthening. The latter was reversible by Vitamin D supplementation in 62.5% of the rats. Testosterone or Vitamin D did not alter vascular histology. Hyperandrogenism increased alpha1-adrenerg mediated vasoconstriction and compromised estrogen-mediated relaxation without altering nitrative stress.