Effects of intrauterine growth restriction on Ca2+-activated force and contractile protein expression in the mesenteric artery of 1-year-old Wistar-Kyoto rats
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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.
KeywordsCa2+-activated force Contractile proteins Intrauterine growth restriction Resistance arteries Vascular smooth muscle
α1C L-type voltage-gated Ca2+-channel
Ethylene glycol bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid
Inositol trisphosphate receptor 1
Intrauterine growth restriction
Myosin light chain
Myosin light chain kinase
Myosin light chain phosphatase
Smooth muscle myosin heavy chain
Myosin light chain phosphatase target subunit 1
Physiological saline solution
Tris buffered saline-Tween
The authors would like to thank Maria Cellini, Heidy Flores, and Aida Youssef for technical assistance, and Simon Watson for statistical analysis design.
All funding provided by La Trobe University; WBS 4.0062.10.35.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
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