From the Department of Surgery (F.T.S., A.C.P., C.D.A.), The University of Mississippi Medical Center, Jackson.
Department of Physiology and Biophysics (F.T.S., J.P.G.), The University of Mississippi Medical Center, Jackson.
Hypertension. 2019 Jan;73(1):162-170. doi: 10.1161/HYPERTENSIONAHA.118.12028.
Preeclampsia is a pregnancy-specific disorder of new-onset hypertension linked to placental ischemia. While obesity is a major risk factor for preeclampsia, not all obese pregnant women develop pregnancy-induced hypertension or preeclampsia. Previously, we reported that placental ischemia-induced hypertension is dependent upon intact signaling of the sympathetic nervous system. Moreover, in various models of obesity, blockade of MC4R (melanocortin-4 receptor) signaling protects against the development of hypertension via suppression of the sympathetic nervous system. Less is known about this pathway during obese pregnancy. Although blockade of MC4R may lead to increased body weight during pregnancy, we tested the hypothesis that placental ischemia-induced hypertension is attenuated in obese MC4R-deficient pregnant rats. On gestational day 14, MC4R wild-type or heterozygous-deficient (MC4R-def) rats were subjected to chronic placental ischemia via the reduced uterine perfusion pressure procedure or Sham surgery then examined on gestational day 19. In Sham MC4R-def versus Sham wild-type pregnant rats, there was increased body weight, fat mass, and circulating leptin levels but they had similar fetus weights. Reduced uterine perfusion pressure reduced fetus weights in both strains. Reduced uterine perfusion pressure increased blood pressure in wild-type rats but this response was significantly attenuated in MC4R-def rats, although blood pressure was elevated in Sham MC4R-def over Sham wild-type. These data indicate that while obese MC4R-def pregnant rats have higher blood pressure during pregnancy, placental ischemia-induced hypertension is attenuated in obese MC4R-def pregnant rats. Thus, obese women with abnormal MC4R signaling may be less susceptible to the development of placental ischemia-induced hypertension.
子痫前期是一种与胎盘缺血相关的新发生的高血压的妊娠特发性疾病。虽然肥胖是子痫前期的主要危险因素，但并非所有肥胖孕妇都会发生妊娠高血压或子痫前期。此前，我们报道胎盘缺血引起的高血压依赖于交感神经系统的完整信号。此外，在各种肥胖模型中，阻断 MC4R（黑素皮质素-4 受体）信号通过抑制交感神经系统来预防高血压的发生。在肥胖妊娠期间，人们对这条途径知之甚少。虽然在怀孕期间阻断 MC4R 可能会导致体重增加，但我们检验了这样一个假设，即肥胖 MC4R 缺陷型怀孕大鼠的胎盘缺血性高血压会减轻。在妊娠第 14 天，MC4R 野生型或杂合缺陷型（MC4R-def）大鼠通过减少子宫灌注压程序或假手术接受慢性胎盘缺血，然后在妊娠第 19 天进行检查。在假手术 MC4R-def 与假手术野生型怀孕大鼠中，体重、脂肪量和循环瘦素水平增加，但胎儿体重相似。减少子宫灌注压降低了两种品系的胎儿体重。减少子宫灌注压增加了野生型大鼠的血压，但这一反应在 MC4R-def 大鼠中明显减弱，尽管在假手术 MC4R-def 大鼠中血压高于假手术野生型大鼠。这些数据表明，虽然肥胖 MC4R-def 怀孕大鼠在怀孕期间血压较高，但肥胖 MC4R-def 怀孕大鼠的胎盘缺血性高血压减轻。因此，MC4R 信号异常的肥胖女性可能不太容易发生胎盘缺血性高血压。
