Women and Children's Health Research Institute, University of Alberta, Edmonton, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, Canada.
J Physiol. 2019 Sep;597(18):4715-4728. doi: 10.1113/JP278223. Epub 2019 Aug 22.
Perinatal iron deficiency causes changes in offspring mesenteric artery function in adulthood, particularly in males, which can be exacerbated by chronic intake of a high salt diet. Perinatal iron deficient male offspring exhibit enhanced conversion of big endothelin-1 to active endothelin-1, coinciding with decreased nitric oxide levels. Perinatal iron deficient male offspring have reduced nitric oxide-mediated endothelial-dependent vasodilatation coincident with increased vascular superoxide levels following consumption of a high salt diet. Perinatal iron deficiency has no apparent effects on vascular function in female offspring, even when fed a high salt diet. These results help us better understand underlying vascular mechanisms contributing to increased cardiovascular risk from perinatal stressors such as iron deficiency.
Pre- and immediate postnatal stressors, such as iron deficiency, can alter developmental trajectories and predispose offspring to long-term cardiovascular dysfunction. Here, we investigated the impact of perinatal iron deficiency on vascular function in the adult offspring, and whether these long-term effects were exacerbated by prolonged consumption of a high salt diet in adulthood. Female Sprague Dawley rats were fed either an iron-restricted or -replete diet prior to and throughout pregnancy. Six weeks prior to experimentation at 6 months of age, adult offspring were fed either a normal or high salt diet. Mesenteric artery responses to vasodilators and vasoconstrictors were assessed ex vivo by wire myography. Male perinatal iron deficient offspring exhibited decreased reliance on nitric oxide with methacholine-induced vasodilatation (interaction P = 0.03), coincident with increased superoxide levels when fed the high salt diet (P = 0.01). Male perinatal iron deficient offspring exhibit enhanced big endothelin-1 conversion to active endothelin-1 (P = 0.02) concomitant with decreased nitric oxide levels (P = 0.005). Female offspring vascular function was unaffected by perinatal iron deficiency, albeit the high salt diet was associated with impaired vasodilation and decreased nitric oxide production (P = 0.02), particularly in the perinatal iron deficient offspring. These findings implicate vascular dysfunction in the sex-specific programming of cardiovascular dysfunction in the offspring by perinatal iron deficiency.
围产期铁缺乏会导致后代肠系膜动脉功能在成年后发生变化，尤其是在雄性中，而长期摄入高盐饮食会使这种情况恶化。围产期缺铁的雄性后代表现出大内皮素-1向活性内皮素-1的转化增强，同时一氧化氮水平降低。围产期缺铁的雄性后代在摄入高盐饮食后，一氧化氮介导的内皮依赖性血管舒张作用减弱，而血管超氧化物水平升高。围产期铁缺乏对雌性后代的血管功能没有明显影响，即使摄入高盐饮食也是如此。这些结果有助于我们更好地理解围产期应激（如缺铁）导致心血管风险增加的潜在血管机制。
产前和产后即刻的应激源，如缺铁，会改变发育轨迹，并使后代易患长期心血管功能障碍。在这里，我们研究了围产期铁缺乏对成年后代血管功能的影响，以及这些长期影响是否会因成年期长期摄入高盐饮食而加剧。雌性 Sprague Dawley 大鼠在怀孕前和怀孕期间均接受铁限制或铁充足饮食。在 6 个月龄时进行实验前的 6 周，成年后代接受正常或高盐饮食。肠系膜动脉对血管扩张剂和血管收缩剂的反应通过电生理记录仪进行离体评估。雄性围产期缺铁的后代在接受高盐饮食时，乙酰胆碱诱导的血管舒张对一氧化氮的依赖性降低（交互作用 P = 0.03），同时超氧化物水平升高（P = 0.01）。雄性围产期缺铁的后代表现出大内皮素-1向活性内皮素-1的转化增强（P = 0.02），同时一氧化氮水平降低（P = 0.005）。围产期铁缺乏对雌性后代的血管功能没有影响，但高盐饮食与血管舒张受损和一氧化氮产生减少有关（P = 0.02），尤其是在围产期缺铁的后代中。这些发现表明，围产期铁缺乏导致的后代心血管功能障碍存在血管功能障碍，且存在性别特异性编程。
