Lower-limb veins are thicker and vascular reactivity is decreased in a rat PCOS model: concomitant vitamin D3 treatment partially prevents these changes

Author:

Várbíró Szabolcs1,Sára Levente1,Antal Péter2,Monori-Kiss Anna2,Tőkés Anna-Mária3,Monos Emil2,Benkő Rita2,Csibi Noémi123,Szekeres Maria4,Tarszabo Robert1,Novak Agnes135,Paragi Péter1,Nádasy György L.2

Affiliation:

1. Second Department of Obstetrics and Gynecology, Faculty of Medicine, Semmelweis University, Budapest, Hungary;

2. Institute of Human Physiology and Clinical Experimental Research, Faculty of Medicine, Semmelweis University, Budapest, Hungary;

3. MTA-SE Tumor Progression Research Group, Second Department of Pathology, Faculty of Medicine, Semmelweis University, Budapest, Hungary;

4. Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary; and

5. Department of Pathology, Bajcsy-Zsilinszky Hospital, Budapest, Hungary

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 NG-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.

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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