Hemmings Denise G, Veerareddy Sukrutha, Baker Philip N, Davidge Sandra T
Department of Obstetrics and Gynecology, Perinatal Research Centre, University of Alberta, Edmonton, Alberta Canada.
Biol Reprod. 2005 Apr;72(4):997-1003. doi: 10.1095/biolreprod.104.035675. Epub 2004 Dec 15.
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 (DR(off)) rat dams. Although no differences were found in pregnancy weight gain, litter size, or fetal weights, placental size was significantly reduced in DR(off) 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 DR(off) 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 DR(off) 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.
流行病学和动物研究结果表明，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，很少有研究考察母体营养不足对怀孕雌性后代血管系统的影响，据我们所知，尚无研究在这些动物模型中考察对血管张力发育至关重要的肌源性反应。因此，我们评估了怀孕雌性后代子宫桡动脉的肌源性反应，以确定孕期饮食限制是否会导致跨代效应。将这些结果与肠系膜动脉的结果进行比较，肠系膜动脉对周围血管阻力有很大影响。在从对照喂养（C(off)）和整体饮食限制（DR(off)）大鼠母鼠的怀孕3个月龄雌性后代分离的动脉中，测量有无一氧化氮合酶（NOS）和前列腺素H合酶（PGHS）抑制剂时的肌源性反应。尽管在孕期体重增加、窝仔数或胎儿体重方面未发现差异，但与C(off)相比，DR(off)的胎盘大小显著减小。与C(off)相比，在DR(off)的子宫动脉而非肠系膜动脉中，在测试的最高压力（110毫米汞柱）下观察到肌源性反应增强。在C(off)中，抑制NOS而非PGHS可显著增加子宫动脉在大于80毫米汞柱压力下的肌源性反应，但有趣的是，与未处理的子宫动脉相比，DR(off)中未出现这种情况。因此，饮食限制的怀孕大鼠母鼠子宫血管功能受损，这会导致其怀孕后代出现类似损害，这可能是不健康怀孕产生跨代效应的一种机制。
