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
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.