Vitamin D deficiency and androgen excess result eutrophic remodeling and reduced myogenic adaptation in small cerebral arterioles in female rats

Abstract

Vitamin D (vitD) insufficiency affects 1 billion people worldwide. Androgen excess (AE) occurs in 8% of fertile females. There are few data about the combined effect of vitD deficiency and AE on the early biomechanical changes of cerebral arterioles in fertile-aged female. Forty-six adolescent female Wistar rats (21–28 day-old, weighing 90–110 g) were grouped randomly in four groups: vitD supplemented groups with and without transdermal testosterone (T) treatment, as well as vitD deficient groups also with and without transdermal T (n = 11 or 12, in all cases). After 8 weeks of treatment, anterior cerebral arterioles (in vivo diameter of 90–130 µm) were obtained and cylindrical segments were examined by pressure arteriography. Myogenic tone, tangential stress and incremental elastic moduli were computed and statistically analyzed. Elastic density was studied on resorcin-fuchsin-stained histological section. VitD deficiency with T treatment resulted in significantly lower inner radii and higher wall thickness values with reduced tangential stress and increased elastic fiber density. VitD deficiency reduced myogenic tone at higher intraluminar pressures (>110 mmHg). Our conclusion is that plasma vitD level is an important factor in the control of myogenic tone in cerebral resistance arteries. AE and vitD deficiency acting parallel induce remodeling of their wall.

摘要：

维生素D (vitD) 不足影响全球10亿人。雄激素过多 (AE) 发生在8%的可生育女性中。关于vitD缺乏与AE对育龄期女性大脑小动脉早期生物力学变化的综合影响的数据很少, 将46只青春期雌性Wistar大鼠 (21-28天,体重90-110g) 随机分成四组:含有和不含经皮睾酮(T) 治疗的vitD补充组,以及含有和不含经皮睾酮 (T) 治疗的vitD缺乏组织 (在所有情况下n = 11或12)。治疗8周后, 取大脑前小动脉 (体内直径90-130mm), 并通过压力动脉造影检查圆柱形段。计算肌源性张力、切向应力和增量弹性模量并进行统计学分析。在间苯二酚-品红染色组织学切片上研究弹性密度。经T处理后的VitD缺乏导致内半径显著降低, 壁厚值增加, 切向应力降低, 弹性纤维密度增加。在较高的腔内压力 (>110mmHg) 下, VitD缺乏降低了肌源性张力。我们的结论是：血浆vitD水平是控制脑阻力动脉肌源性张力的重要因素。AE和vitD缺乏平行作用, 诱导其细胞壁的重塑。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• Androgen excess
• vitD deficiency
• cerebrovascular disease
• rodent model
• anterior cerebral artery

Acknowledgements

The authors express their gratitude to Eszter Urbán, MD, and Andrea Heinzlmann, MD, PhD, for the kind help in histological analysis of cerebral artery sections, Mrs. Ildikó Murányi for her devoted technical assistance and to István Dóczi DPharm for pharmaceutical advices.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by grants from OTKA-PD 113022, by the Dean of the Medical Faculty, Semmelweis University Budapest and by the Hungarian Hypertension Society.