Flanigan Emily G, Farman Gerrie P, Dennis Melissa R, Wollman Lila, Van Den Berg Marloes, Granzier Henk, Banek Christopher T, Fregosi Ralph F
Department of Physiology, College of Medicine, The University of Arizona, Tucson, Arizona, United States.
Department of Cellular & Molecular Medicine, College of Medicine, The University of Arizona, Tucson, Arizona, United States.
Am J Physiol Heart Circ Physiol. 2024 Dec 1;327(6):H1442-H1454. doi: 10.1152/ajpheart.00558.2024. Epub 2024 Oct 25.
Here we test the hypothesis that continuous nicotine exposure throughout pre- and postnatal development (developmental nicotine exposure, DNE) alters the cardiovascular structure and function in neonatal and juvenile rats. Echocardiography showed that DNE reduced left ventricular mass, left ventricular outflow tract (LVOT) diameter, and posterior wall thickness, but only in females. Both male and female DNE rats had a lower end-systolic volume, higher ejection fraction, and increased fractional shortening, with unchanged stroke volume and cardiac output. Left ventricular single cardiac myocytes from male and female DNE animals exhibited increased calcium-evoked maximal tension with no effect on EC. Tail-cuff plethysmography in awake rats showed that DNE males had lower systolic blood pressure and higher heart rate than control males. No significant changes in preload, afterload, or the in vitro renal artery response to vasodilators were observed. The results suggest that DNE enhances myocyte tension-generating capacity, possibly compensating for an unknown developmental insult, which may differ in males and females. Although this adaptation maintains normal resting cardiac function, it may lead to reduced cardiac reserve, increased energy demand, and elevated oxidative stress, potentially compromising both short- and long-term cardiovascular health in developing neonates. Developmental nicotine exposure (DNE) induced cardiovascular changes in neonatal/juvenile rats. Relative to controls, females had reduced left ventricular mass and dimensions, while both sexes had increased ejection fraction and fractional shortening. DNE increased calcium-evoked tension in cardiac myocytes, suggesting an adaptive mechanism as resting cardiac output was preserved. Despite normal resting function, these changes may reduce cardiac reserve, potentially compromising long-term cardiovascular health. These novel findings highlight how DNE disrupts cardiovascular development and function.
在此，我们检验了这样一种假设：在产前和产后整个发育过程中持续暴露于尼古丁（发育性尼古丁暴露，DNE）会改变新生和幼年大鼠的心血管结构与功能。超声心动图显示，DNE降低了左心室质量、左心室流出道（LVOT）直径和后壁厚度，但仅在雌性大鼠中出现这种情况。雄性和雌性DNE大鼠的收缩末期容积均较低，射血分数较高，缩短分数增加，而每搏输出量和心输出量不变。来自雄性和雌性DNE动物的左心室单个心肌细胞表现出钙诱发的最大张力增加，而对EC无影响。清醒大鼠的尾袖体积描记法显示，DNE雄性大鼠的收缩压低于对照组雄性大鼠，心率高于对照组雄性大鼠。未观察到前负荷、后负荷或体外肾动脉对血管扩张剂反应的显著变化。结果表明，DNE增强了心肌细胞产生张力的能力，可能是对一种未知发育损伤的代偿，而这种损伤在雄性和雌性中可能有所不同。尽管这种适应性维持了正常的静息心脏功能，但它可能导致心脏储备减少、能量需求增加和氧化应激升高，从而可能损害发育中新生儿的短期和长期心血管健康。发育性尼古丁暴露（DNE）在新生/幼年大鼠中诱发了心血管变化。相对于对照组，雌性大鼠的左心室质量和尺寸减小，而两性的射血分数和缩短分数均增加。DNE增加了心肌细胞中钙诱发的张力，这表明存在一种适应性机制，因为静息心输出量得以保留。尽管静息功能正常，但这些变化可能会降低心脏储备，从而可能损害长期心血管健康。这些新发现凸显了DNE如何破坏心血管发育和功能。
