Lower-limb veins are thicker and vascular reactivity is decreased in a rat PCOS model: concomitant vitamin D₃treatment partially prevents these changes

Abstract

Polycystic ovary syndrome (PCOS) causes vascular damage to arteries; however, there are no data for its effect on veins. Our aim was to clarify the effects of dihydrotestosterone (DHT)-induced PCOS both on venous biomechanics and on pharmacological reactivity in a rat model and to test the possible modulatory role of vitamin D3 (vitD). PCOS was induced in female Wistar rats by DHT treatment (83 μg/day, subcutaneous pellet). After 10 wk, the venous biomechanics, norepinephrine (NE)-induced contractility, and acetylcholine-induced relaxation were tested in saphenous veins from control animals and from animals treated with DHT or DHT with vitD using pressure angiography. Additionally, the expression levels of endothelial nitric oxide synthase (eNOS) and cyclooxygenase (COX-2) were measured using immunohistochemistry. Increased diameter, wall thickness, and distensibility as well as decreased vasoconstriction were detected after the DHT treatment. Concomitant vitD treatment lowered the mechanical load on the veins, reduced distensibility, and resulted in vessels that were more relaxed. Although there was no difference in the endothelial dilation tested using acetylcholine (ACh), the blocking effect of N(G)-nitro-l-arginine methyl ester (l-NAME) was lower and was accompanied by lower COX-2 expression in the endothelium after the DHT treatment. Supplementation with vitD prevented these alterations. eNOS expression did not differ among the three groups. We conclude that the hyperandrogenic state resulted in thicker vein walls. These veins showed early remodeling and altered vasorelaxant mechanisms similar to those of varicose veins. Alterations caused by the chronic DHT treatment were prevented partially by concomitant vitD administration.

Gender, hyperandrogenism and vitamin D deficiency related functional and morphological alterations of rat cerebral arteries

“…In our study, however, neither VDD nor androgen excess alone caused alterations in vessel lumen and wall thickness of female rats, indicating that neither disorder alone causes remodeling in the cerebral arteries of females, at least not within 8 weeks. On the contrary, some studies report that androgen excess leads to the alteration of either diameter or wall thickness in peripheral vessels [31–33], therefore the impact of hyperandrogenism on vascular remodeling may depend on vessel type. Surprisingly, in males the endogenous physiological androgen level together with VDD decreased the lumen and increased the wall thickness of cerebral arteries.…”

Effects of Gender and Vitamin D on Vascular Reactivity of the Carotid Artery on a Testosterone-Induced PCOS Model

“…Furthermore, a vitamin D-deficient state caused enhanced testosterone-induced tone (opposite calculation to relaxation) in the cerebral arteries of male rats [55]. Despite the fact that vitamin D deficiency/supplementation had no significant effect on testosterone-induced relaxation in our PCOS rats, it is known from the literature that vitamin D supplementation can help restore vascular reactivity damaged by PCOS [52,[55][56][57][58][59]. Endothelial functions improved with vitamin D supplementation in the hyperandrogenic state [56,57,59].…”