Effects of vitamin D3 derivative – calcitriol on pharmacological reactivity of aortic rings in a rodent PCOS model

• Published in: Pharmacological reports Vol. 65; no. 2; pp. 476 - 483
• Main Authors: Masszi, Gabriella, Novak, Agnes, Tarszabo, Robert, Horvath, Eszter Maria, Buday, Anna, Ruisanchez, Eva, Tokes, Anna-Maria, Sara, Levente, Benko, Rita, Nadasy, Gyorgy L., Revesz, Csaba, Hamar, Peter, Benyó, Zoltán, Varbiro, Szabolcs
• Format: Journal Article
• Language: English
• Published: Cham Elsevier B.V 2013; Springer International Publishing
• Subjects: Acetylcholine - pharmacology; Animals; aorta; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; calcitriol; Calcitriol - pharmacology; DHT; Dihydrotestosterone - toxicity; Disease Models, Animal; Drug Safety and Pharmacovigilance; Female; Indomethacin; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Norepinephrine - pharmacology; PCOS; Pharmacotherapy; Pharmacy; Polycystic Ovary Syndrome - drug therapy; Polycystic Ovary Syndrome - physiopathology; Rats; Rats, Wistar; vascular reactivity; Vasoconstriction - drug effects; Vasodilation - drug effects; vitamin D3; DHT; NO; PCOS; calcitriol; vitamin D3; vascular reactivity; aorta; vitamin D
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/S1734-1140(13)71023-5

The aim of this study was to examine the effects of the hyperandrogenic state in dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS), the vascular responses to different vasoactive agents, and the modulatory role of vitamin D3. APCOS model was induced by DHT application in 20 femaleWistar rats. Ten of the DHT treated rats simultaneously received calcitriol treatment. After 10 weeks, myographs were used to test the reactivity of isolated thoracic aortic rings to norepinephrine and acetylcholine. Thereafter, the vascular rings were incubated with the NO-synthase blocker (nitro-L-arginine methyl ester) or the cyclooxygenase inhibitor (indomethacin) for 20min, and the effects of norepinephrine and acetylcholine were re-evaluated. Norepinephrine-induced vasoconstriction was enhanced after DHT treatment, but this effect was attenuated by calcitriol administration. Vasorelaxation of DHT-treated thoracic aortic rings was impaired, but this could be partly reversed by calcitriol application. Impaired NO-dependent vasorelaxation in DHT-treated animals was mostly reversed by concomitant calcitriol administration, but this effect was diminished by prostanoid-dependent vasoconstriction. These studies show that the enhanced sensitivity to vasoconstrictors and impaired NO-dependent vasorelaxation in hyperandrogenic PCOS rats could be partially reversed by calcitriol treatment.