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Effects of intrauterine growth restriction on Ca2+-activated force and contractile protein expression in the mesenteric artery of 1-year-old Wistar-Kyoto rats.
Journal of Physiology and Biochemistry ( IF 3.7 ) Pub Date : 2020-01-11 , DOI: 10.1007/s13105-020-00724-6
Michael J Christie 1 , Tania Romano 1 , Robyn M Murphy 2 , Giuseppe S Posterino 1
Affiliation  

Intrauterine growth restriction (IUGR) affects vascular reactivity in older rats, but at present the causative factors for this change are unknown. Therefore, we investigated downstream events associated with vascular reactivity, specifically, Ca2+-regulated force production and shifts in contractile protein content. The mesenteric artery from male and female 1-year-old Wistar-Kyoto rats was examined using two distinct experimental growth restriction models. Uterine ligation surgery restriction or a sham surgery was conducted at day 18 of pregnancy, whilst a food restriction diet (40% control diet) began on gestational day 15. Extracellular vascular reactivity was studied using intact mesenteric arteries, which were subsequently chemically permeabilized using 50 μM β-escin to examine Ca2+-activated force. Peak contractile responses to a K+-induced depolarization and phenylephrine were significantly elevated due to an increase in maximum Ca2+-activated force in the male surgery restricted group. No changes in contractile forces were reported between female experimental groups. Sections of mesenteric artery were examined using western blotting, revealing IUGR increased the relative abundance of the voltage-gated Ca2+ channel, inositol-1,4,5-trisphosphate receptor and myosin light chain kinase, in both male growth restricted groups, whereas no changes were seen in females. These findings demonstrate for the first time in 1-year-old rats that changes in vascular reactivity due to IUGR are caused by a change in Ca2+-activated force and shifts in important contractile protein content. These changes affect the Wistar-Kyoto rat in a sex-specific and maternal insult-dependent manner.

中文翻译:

宫内生长受限对1岁Wistar-Kyoto大鼠肠系膜动脉Ca2 +激活力和收缩蛋白表达的影响。

宫内生长受限(IUGR)影响老年大鼠的血管反应性,但目前尚不清楚这种变化的病因。因此,我们研究了与血管反应性相关的下游事件,特别是Ca 2+调节的力产生和收缩蛋白含量的变化。使用两个不同的实验性生长限制模型检查了雄性和雌性1岁Wistar-Kyoto大鼠的肠系膜动脉。在妊娠第18天进行子宫结扎手术限制或假手术,而在妊娠第15天开始饮食限制饮食(40%对照饮食)。使用完整的肠系膜动脉研究细胞外血管反应性,随后使用50进行化学通透μMβ-七叶皂苷检查Ca 2+力。在男性手术受限组中,由于最大Ca 2+激活力的增加,对K +诱导的去极化和去氧肾上腺素的峰值收缩反应显着提高。女性实验组之间未见收缩力变化的报道。使用蛋白质印迹法检查了肠系膜动脉的切片,发现在两个男性生长受限组中,IUGR均增加了电压门控的Ca 2+通道,肌醇-1,4,5-三磷酸受体和肌球蛋白轻链激酶的相对丰度,而女性未见变化。这些发现首次证明1岁大的大鼠因IUGR引起的血管反应性改变是由Ca 2+的改变引起的激活的力和重要收缩蛋白含量的变化。这些变化以性别特异性和母体损伤依赖性方式影响Wistar-Kyoto大鼠。
更新日期:2020-01-11
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