Effects of vitamin d on carotid structure and function in a rat model of polycystic ovary syndrome

Objective: Polycystic ovary syndrome (PCOS) is a common gynecological disorder of endocrine origin that can be associated with increased cardiovascular morbidity and vitamin D deficiency. The effects of vitamin D deficiency on cardio-metabolic risk in PCOS have been shown in previous studies. In the present experiments, we investigated the effect of vitamin D supplementation in light of optimal vitamin D intake on rat carotid artery function in a rat model of PCOS. Our aim was to investigate the effects of vitamin D supplementation and hyperandrogenism on functional and morphological changes of the carotid artery. Design and method: Adolescent female Wistar rats were provided with normal (C: 1000 IU/day/kg/week) or increased (D: 3000 IU/day/kg/week) vitamin D intake for 8 weeks. In half of these animals hyperandrogenism was induced by testosterone treatment (T and T+D: daily cutaneous testosterone: 3.3 mg/100 g) (N=8 in all 4 groups). After 8 weeks, carotid arteries were isolated and phenylephrine (Phe)-induced contraction and acetylcholine (Ach)-induced relaxation of the vascular rings were examined by myography. Wall thickness and intima-media ratio were determined in hematoxylin-eosin stained tissue sections, vessel wall connective tissue fiber density in resorcin-fuchsin stained sections, and vessel smooth muscle densitometry by -αsmooth muscle actin immunostaining. Results: The hyperandrogenic state induced a decreased contractility as a response to Phe (10-6 M Phe expressed in the % of K+-induced contraction: T: 62±22% p<0.001 vs. C: 116±33%; D: 101±39%), that was reversible by Vitamin D treatment (T+D: 95±16%, ns.). Endothelium-mediated relaxation did not differ between groups. Hyperandrogenic state significantly increased vessel wall thickness (T: 74.81 ±4.48 μm, p<0.05 vs. C: 57.92±2.96 μm; D: 53.21±10.8 μm), which was prevented by Vitamin D (58.99±8.75 μm, ns.) whereas intima-media ratio did not change. No significant differences were found for smooth muscle actin and connective tissue fiber density. Conclusions: Our results suggest that the hyperandrogenism increased vessel wall thickness and, in comparison to media thickness the alpha1-adrenerg sensitivity decreased, leading to a limited capacity of regulation. The morphological remodeling of the vascular wall induced by testosterone treatment did not cause significant endothelial functional changes yet.