![]() Vascular smooth muscle cells (VSMC) are not terminally differentiated (Owens 1995), they retain enormous plasticity to fulfil several functions, switching between a contractile and proliferating/synthetic phenotype (Owens et al. Reducing MLCP activity while increasing MLCK activity through a rise in i tilts the balance toward generating extra force. Vascular smooth muscle contraction is primarily controlled by the level of intracellular which regulates the balance of myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) activities, biochemically controlling the Ca 2+–tension relationship through increasing or decreasing phosphorylation of the myosin light chain (MLC) (Kitazawa and Somlyo 1990 Kitazawa et al. However, it is unclear whether these observed changes in vascular sensitivity are driven by changes in receptor number/activity or by changes in downstream events that lead to force development specifically, the Ca 2+‐regulated activation of the contractile apparatus. 2007), which contribute to the development of cardiovascular disease in adulthood.Įvidence of an altered extracellular vascular responsiveness to certain vasoactive chemicals has been widely recognized in several IUGR rat models (Williams et al. 2001) and increased arterial wall stiffness (Khorram et al. 2012), endothelial dysfunction (Goodfellow et al. Several studies utilizing these IUGR animal models have reported changes to vascular smooth muscle responsiveness (Williams et al. Maternal dietary manipulations, such as a food restriction (FR) diet, are used to imitate this condition in animal studies (Williams et al. In the developing world, maternal malnutrition is the major cause of IUGR, resulting from lasting nutrient deficiency of the pregnant mother negatively affecting the growing fetus (Bergmann et al. ![]() A bilateral uterine vessel ligation surgery restriction (SR) is often used to mimic this condition in animal studies (Wlodek et al. 1998).Ī common cause of IUGR in Western society is uteroplacental insufficiency, occurring when remodeling of placental spiral arteries is incomplete thus, reducing both nutrient and oxygen availability to the developing fetus (Khong et al. IUGR is a manifestation of several maternal, paternal and fetal factors, arising from genetic or environmental issues, resulting in poor growth of the developing fetus (Peleg et al. Results from this study suggest that IUGR alters the mesenteric artery reactivity due to a decrease in maximum Ca 2+‐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.Įpidemiological and experimental studies have recognized that IUGR or the failure of an infant to achieve their genetic potential for growth are prone to developing diseases in later life, including cardiovascular diseases such as hypertension and coronary heart disease (Barker 1994 Gluckman and Hanson 2004 McMillen and Robinson 2005). 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. Vascular responsiveness was unchanged between female experimental groups. ![]() Peak responsiveness to a K +‐induced depolarization was decreased ( P ≤ 0.05) due to a reduction in maximum Ca 2+‐activated force ( P ≤ 0.05) in both male growth restricted experimental groups. At 6‐months of age, vascular responsiveness of intact mesenteric arteries was studied, before chemically permeabilization using 50 μmol/L β‐escin to investigate Ca 2+‐activated force. 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. This study investigated the effects of IUGR on Ca 2+‐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. 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, Ca 2+‐regulated activation of the contractile apparatus or a shift in contractile protein content.
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