Semmelweis University, Hungary
Levente Sara M.D., J.D. has completed Ph.D and postdoctoral studies from Semmelweis University Budapest in 2012. His thesis was the “Alterations of Arteriolar Reactivity in a Rat Polycystic Ovary Syndrome Model”. He is Ob&Gyn specialist and assistant professor of the Semmelweis University. His research field is the cardiovascular alterations, pharmacological reactivity of arteries and veins in PCOS.
Our aim was to clarify the effects of dihydrotestosterone (DHT)-induced polycystic ovary syn-drome (PCOS) on insulin-dependent vasodilatation of thoracic aorta and resistance arteries. We also aimed to investigate the possible modulatory role of vitamin D3 (vitD) in an animal model.
Design: In this controlled experimental animal study thirty female Wistar rats were divided into groups at age of 21-28 days. Twenty of them were subjected to dihydrotestosterone (DHT) treat-ment (83 µg/day); ten of them also received parallel vitD treatment (120 ng/100 g/week). Oral glu-cose 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. Thoracic aorta segments were also isolated. Insulin-dependent vasodilation of the aorta rings in normal Krebs-Ringer solution was compared to the response of rings treated with NO-synthase (by nitro-L-arginine methyl ester) or cyclooxygenase (by indomethacin) blockade.
Results: DHT treatment increased the passive diameter of resistance arterioles, lowered norepi-nephrine-induced contraction, reduced acetylcholine-induced and insulin-induced dilation. VitD treatment restored insulin relaxation and norepinephrine-induced contractility; in contrast, it failed to alter NO-dependent relaxation of arterioles. Insulin-dependent vasorelaxation of aortic rings de-creased in both DHT-treated groups independent of vitD treatment. Impaired NO-relaxation and enhanced prostanoid contraction of the aorta rings were observed.
Conclusion: VitD treatment prevented systemic insulin resistance. In DHT-treated rats, in addition to metabolically proven insulin resistance, decreased insulin-induced vasorelaxation was observed and was improved by vitD 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 vitD treatment. DHT treatment also caused deterioration of insulin-induced vasodilation on aorta rings. VitD did not influence vascular insulin resistance of the aorta. Controlling insulin resistance with vitD alone did not resolve the endothelial dysfunction of the aorta caused by the hyperandrogenic state.