Vitamin D Deficiency Cause Gender Specific Alterations of Renal Arterial Function in a Rodent Model

Abstract

Vitamin D deficiency shows positive correlation to cardiovascular risk, which might be influenced by gender specific features. Our goal was to examine the effect of Vitamin D supplementation and Vitamin D deficiency in male and female rats on an important hypertension target organ, the renal artery. Female and male Wistar rats were fed with Vitamin D reduced chow for eight weeks to induce hypovitaminosis. Another group of animals received normal chow with further supplementation to reach optimal serum vitamin levels. Isolated renal arteries of Vitamin D deficient female rats showed increased phenylephrine-induced contraction. In all experimental groups, both indomethacin and selective cyclooxygenase-2 inhibition (NS398) decreased the phenylephrine-induced contraction. Angiotensin II-induced contraction was pronounced in Vitamin D supplemented males. In both Vitamin D deficient groups, acetylcholine-induced relaxation was impaired. In the female Vitamin D supplemented group NS398, in males the indomethacin caused reduced acetylcholine-induced relaxation. Increased elastic fiber density was observed in Vitamin D deficient females. The intensity of eNOS immunostaining was decreased in Vitamin D deficient females. The density of AT1R staining was the highest in the male Vitamin D deficient group. Although Vitamin D deficiency induced renal vascular dysfunction in both sexes, female rats developed more extensive impairment that was accompanied by enzymatic and structural changes.

Vitamin D Deficiency and Gender Alter Vasoconstrictor and Vasodilator Reactivity in Rat Carotid Artery

“…Previous results from our research group also suggest that gender-specific alterations of vascular function and structure can be observed in the renal and cerebral arteries of vitamin D deficient rats [ 16 , 17 ]. In the anterior cerebral artery, vitamin D deficiency resulted in increased wall thickness and testosterone-induced contraction only in male rats [ 16 ].…”

“…In males the myogenic tone and the reaction to thromboxane A2 agonist are also more pronounced on coronary resistance arteries [ 22 ]. On the contrary, no gender differences were found in renal arteries for Phe-induced contraction [ 17 ], and there were also no gender differences in endothelium-dependent vasoconstriction of the popliteal artery [ 23 ]. In our current study, we found significantly higher phenylephrine-induced vasoconstriction on carotid arterial rings of male animals independently from their vitamin D status.…”

“…In coronary arteries of male animals, vitamin D deficiency decreased the vascular reactivity to thromboxane A2 and sexual steroids (estrogen and testosterone) [ 34 ]. On the other hand, in renal arteries, we saw increased Phe-induced contraction only in female, but not in male rats [ 17 , 26 ]. Vitamin D can inhibit TP receptor expression [ 35 ] and the increased TP immunolabeling intensity observed in vitamin D deficient males may reflect the lack of this suppressing effect, contributing to their increased Phe-induced contraction.…”

“…In renal arteries vitamin D deficiency led to impaired acetylcholine (Ach)-induced relaxation in both genders, whereas increased phenylephrine contraction was only found in male animals. Vascular function measurements in the presence of cyclooxygenase (COX) inhibitor and the immunohistochemical labeling of endothelial nitric oxide synthase (eNOS) in these vessels suggest that eNOS and prostanoid pathways may play a role in the gender-specific vascular dysfunction in vitamin D deficiency [ 17 ].…”

Influence of Vitamin D on the Vasoactive Effect of Estradiol in a Rat Model of Polycystic Ovary Syndrome

“…Vitamin D can activate eNOS not only through the increase of intracellular calcium levels but via the PI3K/Akt pathway [12]. Prior studies reported that vitamin D deficiency decreased eNOS level and vasorelaxation in rat renal arteries but vitamin D treatment was able to improve acetylcholine-induced relaxation [13].…”