SEX SPECIFIC CHANGES OF CAROTID ARTERIAL FUNCTION IN RESPONSE TO VITAMIN D DEFICIENCY

Abstract

Objective: Male sex and Vitamin D deficiency is associated with increased ischemic stroke risk that may be partially explained by local changes of circulatory control. Our aim was to examine the vascular reactivity and histological changes of isolated carotid artery of female and male rats in Vitamin D deficient and Vitamin D supplemented state. Design and method: Female and male Wistar rats were fed with vitamin D reduced rat chow for eight weeks. Another group received normal chow with further supplementation of vitamin D. Phenylephrine induced contraction, acetylcholine and estrogen induced relaxation of carotid arteries was examined by wire myography. Elastic fiber density was evaluated on resorcin-fuchsin stained tissue sections. Smooth muscle cell actin (SMA), thromboxane A2 receptor and endothelial nitric oxide synthase (eNOS) density and protein tyrosine nitration (NT) was measured by immunohistochemistry. Results: Both male sex and vitamin D deficiency resulted in increased phenylephrine induced contraction. Inhibition of cyclooxygenases by indomethacin increased the degree of contraction only in vitamin D supplemented females. Male gender was associated with reduced acetylcholine induced relaxation, and it was not altered by vitamin D deficiency. Indomethacin increased relaxation in male vessels. Estrogen induced relaxation was significantly reduced by vitamin D deficiency in female but not in male animals. Vitamin D deficiency resulted in reduced elastic fiber density in female, but decreased smooth muscle cell actin density in male rats. Thromboxane A2 receptor density was increased in vitamin D deficient males. NT immunohistochemistry was low in both male group, whereas eNOS was reduced in vitamin D deficient males. Conclusions: In rats male gender was associated with increased phenylephrine induced contraction and reduced acetylcholine induced relaxation of the carotid artery. Vitamin D deficiency caused increased contraction in both sexes; did not change acetylcholine induced relaxation, but reduced the estrogen induced relaxation in female arteries. These functional differences were accompanied with sex specific histological changes of the vessel. The observed sex specific properties and responses of carotid artery to vitamin D deficiency may play a role in the gender difference of cardiovascular and stroke risk.