Arteriolar insulin resistance in a rat model of polycystic ovary syndrome

ObjectiveTo investigate the vascular dysfunction caused by insulin resistance in polycystic ovary syndrome (PCOS) and the effectiveness of vitamin D in an animal model.DesignControlled experimental animal study.SettingAnimal laboratory at a university research institute.Animal(s)Thirty female Wistar rats.Intervention(s)Rats were divided into groups at age 21–28 weeks. Twenty of them were subjected to dihydrotestosterone (DHT) treatment (83 μg/d); ten of them also received parallel vitamin D treatment (120 ng/100 g/wk). Oral glucose tolerance tests with insulin level measurements were performed. Gracilis arterioles were tested for their contractility as well as their nitric oxide (NO)–dependent and insulin-induced dilation using pressure arteriography.Main Outcome Measure(s)Several physiologic parameters, glucose metabolism, and pressure arteriography.Result(s)DHT treatment increased the passive diameter of resistance arterioles, lowered norepinephrine-induced contraction (30.1 ± 4.7% vs. 8.7 ± 3.6%) and reduced acetylcholine-induced (122.0 ± 2.9% vs. 48.0 ± 1.4%) and insulin-induced (at 30 mU/mL: 21.7 ± 5.3 vs. 9.8 ± 5.6%) dilation. Vitamin D treatment restored insulin relaxation and norepinephrine-induced contractility; in contrast, it failed to alter NO-dependent relaxation.Conclusion(s)In DHT-treated rats, in addition to metabolically proven insulin resistance, decreased insulin-induced vasorelaxation was observed and was improved by vitamin D treatment without affecting NO-dependent relaxation. The reduction in insulin-induced dilation of arterioles is an important as yet undescribed pathway of vascular damage in PCOS and might explain the clinical effectiveness of vitamin D treatment.