Arteriolar insulin resistance in a rat model of polycystic ovary syndrome

Abstract

Objective: To investigate the vascular dysfunction caused by insulin resistance in polycystic ovary syndrome (PCOS) and the effectiveness of vitamin D in an animal model. Design: Controlled experimental animal study. Setting: Animal 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 mg/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 AE 4.7% vs. 8.7 AE 3.6%) and reduced acetylcholine-induced (122.0 AE 2.9% vs. 48.0 AE 1.4%) and insulin-induced (at 30 mU/mL: 21.7 AE 5.3 vs. 9.8 AE 5.6%) dilation. Vitamin D treatment restored insulin relaxation and norepinephrine-induced contractility; in contrast, it failed to alter NO-dependent relaxation.

Immunohistochemical evaluation of proliferation, apoptosis and steroidogenic enzymes in the ovary of rats with polycystic ovary

“…3,4 It is possible to mimic PCOS in rats by inducing continuous light for long periods, so they enter a state of permanent estrus, without ovulation, presence of ovarian cysts, as well as increased circulating estrogens and androgens, as well as insulin resistance. 5 In previous work we found the presence of ovarian cysts in the ovary of rats submitted to continuous light, the absence of corpora lutea and a large concentration of interstitial cells, which we reported as being derived from theca interna due to the degeneration of ovarian cysts. Moreover, we found a significant increase in serum levels of testosterone and estradiol.…”

Altered insulin-induced relaxation of aortic rings in a dihydrotestosterone-induced rodent model of polycystic ovary syndrome

“…In this study, we tested the two essential mechanisms regulating vascular tone: the relaxing capacity under pretreatment with L-N G -nitroarginine methyl ester hydrochloride (L-NAME, i.e., NO synthase blocker) or indomethacin (i.e., cyclooxygenase blocker). Earlier, we demonstrated the positive effect of vitamin D on systemic insulin resistance (14). The DHT-dependent reduction of insulin-induced vasorelaxation found in small arteries was improved by parallel vitamin D administration (14).…”

“…The vitamin D was given subcutaneously as previously described by Przybilski et al We administered a weekly-for 10 weeks-instead of daily dosage (13,14) of vitamin D to reduce the stress to the animals. 1,25(OH) 2 -vitamin D 3 was chosen (injectable Calcijex, 2 mg/ mL; Abbott Laboratories) because this is the active form of vitamin D and the action of other forms depends on liver and renal function (13,14). The control group and ten of the DHT-treated animals received vitamin D vehicle (saline solution) subcutaneously.…”

“…Earlier, we demonstrated the positive effect of vitamin D on systemic insulin resistance (14). The DHT-dependent reduction of insulin-induced vasorelaxation found in small arteries was improved by parallel vitamin D administration (14). We sought to demonstrate a similar phenomenon in large vessels, such as the aorta, in a HAF rat model.…”

“…A similar chronic vitamin D therapy prevented heart failure and left ventricular hypertrophy in adolescent heart failure-prone spontaneously hypertensive rats (SHR) (13). Previously, we reported that after 70 days of DHT administration, the insulin-induced vasorelaxation decreased in the small arteries of HAF rats (14). This effect was prevented by a concomitant weekly dosage of vitamin D. Because nitric oxide (NO)-dependent relaxation, which deteriorated with chronic DHT treatment, was not influenced by vitamin D, other mechanisms of compensation might be involved.…”