Prenatal cold exposure causes hypertension in offspring by hyperactivity of the sympathetic nervous system
Prenatal cold exposure causes hypertension in offspring by hyperactivity of the sympathetic nervous system
复制标题
产前寒冷暴露导致交感神经系统过度活跃，导致后代高血压
DOI：
10.1042/cs20190254
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发表时间：
2019-05-15
期刊：
影响因子：
6
通讯作者：
Zeng, Chunyu
中科院分区：
文献类型：
--
作者：
Chen, Ken;Sun, Dongdong;Zeng, Chunyu
环境温度对血压的变化有一定影响。母体冷应激可影响子代的生理表型，包括血压升高。在本研究中，我们发现，暴露于寒冷的母鼠的成年后代的收缩压和舒张压增加，尿量和钠排泄量减少，伴随着心率和心率变异性增加，继发于交感神经系统活动增加。去肾神经或肾上腺素能受体阻断可降低血压并增加钠排泄。外周交感神经活动的增加可归因于中枢神经系统，因为给予可乐定（一种中枢作用的α2肾上腺素能受体激动剂），使产前冷暴露后代的血压降低程度大于对照后代。此外，这些产前冷暴露的后代有下丘脑室旁核（PVN）的障碍，因为磁共振波谱显示减少N-乙酰天冬氨酸和增加胆碱和肌酸的比例在PVN。进一步的研究发现，产前冷暴露损害了抑制性和兴奋性神经元之间的平衡。这导致PVN过度激活，这与增强的PVN-血管紧张素II 1型（AT 1）受体表达和功能有关。在PVN中微量注射AT 1受体拮抗剂氯沙坦在产前冷暴露的对照后代中降低血压的程度更大。本研究提供了证据，过度活跃的外周和中枢交感神经系统在产前冷诱发高血压的发病机制。阻断室旁核AT 1受体可能是治疗该类高血压的关键。
Environmental temperature plays a role in the variation of blood pressure. Maternal cold stress could affect the physiological phenotype of the offspring, including blood pressure elevation. In the present study, we found that adult offspring of dams exposed to cold have increased systolic and diastolic blood pressure, and decreased urine volume and sodium excretion, accompanied by increased heart rate and heart rate variability, secondary to increased activity of the sympathetic nervous system. Renal denervation or adrenergic receptor blockade decreased blood pressure and increased sodium excretion. The increase in peripheral sympathetic nerve activity can be ascribed to the central nervous system because administration of clonidine, a centrally acting α2 adrenergic receptor agonist, lowered blood pressure to a greater degree in the prenatal cold-exposed than control offspring. Moreover, these prenatal cold-exposed offspring had hypothalamic paraventricular nucleus (PVN) disorder because magnetic resonance spectroscopy showed decreased N-acetylaspartate and increased choline and creatine ratios in the PVN. Additional studies found that prenatal cold exposure impaired the balance between inhibitory and excitatory neurons. This led to PVN overactivation that was related to enhanced PVN-angiotensin II type 1 (AT1) receptor expression and function. Microinjection of the AT1 receptor antagonist losartan in the PVN lowered blood pressure to a greater extent in prenatal cold-exposed that control offspring. The present study provides evidence for overactive peripheral and central sympathetic nervous systems in the pathogenesis of prenatal cold-induced hypertension. Central AT1 receptor blockade in the PVN may be a key step for treatment of this type hypertension.