Increased myogenic responses in uterine but not mesenteric arteries from pregnant offspring of diet-restricted rat dams
Increased myogenic responses in uterine but not mesenteric arteries from pregnant offspring of diet-restricted rat dams
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DOI：
10.1095/biolreprod.104.035675
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发表时间：
2005-04-01
影响因子：
3.6
通讯作者：
Davidge, ST
中科院分区：
文献类型：
--
作者：
Hemmings, DG;Veerareddy, S;Davidge, ST
流行病学和动物研究的结果表明，子宫内生长不良与成年后代的心血管疾病之间存在联系。然而，很少有研究探讨母体营养不良对妊娠雌性后代血管系统的影响，据我们所知，没有研究探讨这些动物模型中对血管张力发育至关重要的肌源性反应。因此，在妊娠雌性后代的子宫桡动脉中评估肌源性反应，以确定妊娠期间的饮食限制是否会导致跨代效应。这些结果进行了比较，在肠系膜动脉，这极大地有助于外周血管阻力。在存在和不存在一氧化氮合酶（NOS）和前列腺素H合酶（PGHS）抑制剂的情况下，在从对照喂养（C-off）和全球饮食限制（DRoff）大鼠母鼠的妊娠、3月龄雌性后代分离的动脉中测量肌源性反应。虽然在妊娠体重增加、窝仔数或胎仔重量方面没有发现差异，但与C-off相比，DRoff组胎盘大小显著降低。与C-off相比，在最高测试压力（110 mm Hg）下，在子宫动脉中观察到肌源性反应增强，但在肠系膜动脉中未观察到。与未经处理的子宫动脉相比，NOS的抑制，而不是PGHS的抑制，在C-off中在压力大于80 mm Hg时显著增加了子宫动脉的肌源性反应，但有趣的是，在DRoff中没有增加。因此，在饮食限制的怀孕大鼠母鼠中，子宫血管功能受损，导致其怀孕后代出现类似的损伤，可能是不健康妊娠的跨代影响发生的机制。
Results of epidemiological and animal studies suggest a link between poor in utero growth and cardiovascular disease in adult offspring. Few studies, however, have examined the effects of maternal undernutrition on the vasculature of pregnant female offspring, and to our knowledge, no studies have examined myogenic responses, which are essential to vascular tone development, in these animal models. Thus, myogenic responses were assessed in radial uterine arteries of pregnant female offspring to determine if diet restriction during pregnancy could contribute to transgenerational effects. These results were compared to those in mesenteric arteries, which greatly contribute to peripheral vascular resistance. Myogenic responses in the presence and absence of inhibitors for nitric oxide synthase (NOS) and prostaglandin H synthase (PGHS) were measured in arteries isolated from pregnant, 3-mo-old female offspring of control-fed (C-off) and globally diet-restricted (DRoff) rat dams. Although no differences were found in pregnancy weight gain, litter size, or fetal weights, placental size was significantly reduced in DRoff compared to C-off. Enhanced myogenic reactivity was observed at the highest pressure tested (110 mm Hg) in uterine, but not in mesenteric, arteries from DRoff compared to C-off. Inhibition of NOS, but not of PGHS, significantly increased myogenic responses in uterine arteries at pressures greater than 80 mm Hg in C-off but, interestingly, not in DRoff compared to untreated uterine arteries. Thus, impaired uterine vascular function in diet-restricted pregnant rat dams, which leads to similar impairment in their pregnant offspring, may be a mechanism through which transgenerational effects of unhealthy pregnancies occur.