Effects of intrauterine growth restriction on Ca2+-activated force and contractile protein expression in the mesenteric artery of 1-year-old Wistar-Kyoto rats

• Published in: Journal of physiology and biochemistry Vol. 76; no. 1; pp. 111 - 121
• Main Authors: Christie, Michael J., Romano, Tania, Murphy, Robyn M., Posterino, Giuseppe S.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.02.2020; Springer Nature B.V
• Subjects: Animal Physiology; Arteries; Biomedical and Life Sciences; Biomedicine; Calcium; Calcium channels (voltage-gated); Calcium ions; Contractility; Depolarization; Diet; Females; Food availability; Human Physiology; Inositol 1,4,5-trisphosphate receptors; Kinases; Myosin; Myosin-light-chain kinase; Nitric oxide; Nutrient content; Original Article; Phenylephrine; Pregnancy; Proteins; Reactivity; Surgery; Uterus; Western blotting; Resistance arteries; Intrauterine growth restriction; activated force; Vascular smooth muscle; Contractile proteins; Ca
• ISSN: 1138-7548; 1877-8755
• DOI: 10.1007/s13105-020-00724-6

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, Ca 2+ -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 Ca 2+ -activated force. Peak contractile responses to a K + -induced depolarization and phenylephrine were significantly elevated due to an increase in maximum Ca 2+ -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 Ca 2+ 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 Ca 2+ -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.