The effect of intrauterine growth restriction on Ca²⁺-activated force and contractile protein expression in the mesenteric artery of adult (6-month-old) male and female Wistar-Kyoto rats

Abstract

Intrauterine growth restriction (IUGR) is known to alter vascular smooth muscle reactivity, but it is currently unknown whether these changes are driven by downstream events that lead to force development, specifically, Ca2+‐regulated activation of the contractile apparatus or a shift in contractile protein content. This study investigated the effects of IUGR on Ca2+‐activated force production, contractile protein expression, and a potential phenotypic switch in the resistance mesenteric artery of both male and female Wistar‐Kyoto (WKY) rats following two different growth restriction models. Pregnant female WKY rats were randomly assigned to either a control (C; N = 9) or food restriction diet (FR; 40% of control; N = 11) at gestational day‐15 or underwent a bilateral uterine vessel ligation surgery restriction (SR; N = 10) or a sham surgery control model (SC; N = 12) on day‐18 of gestation. At 6‐months of age, vascular responsiveness of intact mesenteric arteries was studied, before chemically permeabilization using 50 μmol/L β‐escin to investigate Ca2+‐activated force. Peak responsiveness to a K+‐induced depolarization was decreased (P ≤ 0.05) due to a reduction in maximum Ca2+‐activated force (P ≤ 0.05) in both male growth restricted experimental groups. Vascular responsiveness was unchanged between female experimental groups. Segments of mesenteric artery were analyzed using Western blotting revealed IUGR reduced the relative abundance of important receptor and contractile proteins in male growth restricted rats (P ≤ 0.05), suggesting a potential phenotypic switch, whilst no changes were observed in females. Results from this study suggest that IUGR alters the mesenteric artery reactivity due to a decrease in maximum Ca2+‐activated force, and likely contributed to by a reduction in contractile protein and receptor/channel content in 6‐month‐old male rats, while female WKY rats appear to be protected.

Intrauterine growth restriction weakens anticontractile influence of NO in coronary arteries of adult rats

“…In our study IUGR did not lead to the changes in maximum active force or diameter of mesenteric arteries. Furthermore, α 1 -adrenergic reactivity of these arteries was not changed by IUGR, that goes in accordance with previously published data 29 , 31 , 32 . Consequently, unaltered arterial responses in IUGR rats were not accompanied by apparent changes in the contribution of Rho-kinase or endothelial NO in the vasomotor control.…”

“…Mesenteric vasculature are often used as a representative vascular bed of systemic circulation, including studies on IUGR animals 27 – 32 . In our study IUGR did not lead to the changes in maximum active force or diameter of mesenteric arteries.…”

Fetal Undernutrition Induces Resistance Artery Remodeling and Stiffness in Male and Female Rats Independent of Hypertension

“…SMC exhibit high plasticity, and phenotypic switch towards a secretory non-contractile phenotype can lead to ECM accumulation. Loss of contractile proteins suggesting this phenotypic switch have been found in MRA from rats exposed to fetal undernutrition and in a rat model of fetal programming induced by uterine artery ligation, although this was observed only in male offspring [ 37 ]. Previous reports in animals exposed to stress factors during intrauterine life have demonstrated alterations in several ECM proteins, including elastin, collagen, and glycosaminoglycans [ 13 , 25 ].…”

Intrauterine Growth Restriction Weakens Anticontractile Influence of NO in Coronary Arteries of Adult Rats 

“…Regulation of mesenteric artery tone of adult animals is not altered by IUGR Mesenteric vasculature are often used as a representative vascular bed of systemic circulation, including studies on IUGR animals [27][28][29][30][31][32] . In our study IUGR did not lead to the changes in maximum active force or diameter of mesenteric arteries.…”