SYMPATHETIC EXCITATORY RESPONSE AT BIRTH

从胎儿到新生儿的过渡与许多因素有关。 生理调节是通过相互作用的神经 和荷尔蒙机制。 随着交货期的延长， 增加肾素-血管紧张素系统的活性， 交感神经流出 然而，对于早产， 交感神经兴奋反应是不存在的，而心血管和代谢 功能受损。最近，产前糖皮质激素的使用 在早产中促进胎儿肺成熟已经显示， 改善出生时心血管反应和刺激交感神经 神经活动，尽管调节这些反应的机制是 不知道。 在成人中，解剖学、生理学和生物化学研究 涉及下丘脑室旁核（PVN） 在心血管调节中，作为前脑输入的主要来源 交感神经系统和耦合的重要环节， 具有中枢自主调节功能的肾素-血管紧张素系统。 基于 根据这些研究，我们假设PVN的功能是 出生时交感神经活动的重要调节器， 血管紧张素II I型（AT 1）受体表达的发育变化 并且PVN内的功能介导这些交感神经反应。 到 为了验证这一假设，本提案旨在a）阐明 室旁核在调节心血管和 出生时的交感神经功能，B）确定 中枢神经系统AT 1受体的成熟变化 功能和c）研究PVN和中枢AT 1受体 参与糖皮质激素增强交感神经兴奋性 出生时的反应 这些研究将增进我们对 发育中的胎儿和新生儿调节交感神经流出， 增加我们对生命早期心血管功能的了解， 可能会导致新的治疗策略的发展，以防止 与全身血流动力学改变相关的发病率和死亡率。

The transition from fetal to newborn life is associated with numerous physiological adjustments which are achieved through interacting neural and hormonal mechanisms. With delivery at term, there are striking increases in the activity of the renin-angiotensin system and sympathetic outflow. However, with premature delivery, the sympathoexcitatory response is absent while cardiovascular and metabolic functions are impaired. Recently, the use of antenatal glucocorticoids in preterm labor to promote fetal lung maturity has been shown to improve cardiovascular responses at birth and stimulate sympathetic nerve activity, although the mechanisms regulating these responses are not known. In adults, anatomic, physiologic and biochemical studies have implicated the paraventricular nucleus (PVN) of the hypothalamus in cardiovascular regulation, being a major source of forebrain input to the sympathetic nervous system and an important link in coupling in the renin-angiotensin system with central autonomic regulation. Based on these studies, we are postulating that the PVN functions as an important regulator of sympathetic activity at birth and that developmental changes in angiotensin II type I (AT1) receptor expression and function within the PVN mediate these sympathetic responses. To test this hypothesis, the present proposal is designed to a) elucidate the physiological role of the PVN in regulating cardiovascular and sympathetic function at birth, b) to determine the influence of maturational changes in brain AT1 receptors on central autonomic function and c) investigate whether the PVN and central AT1 receptors participate in glucocorticoid augmentation of the sympathoexcitatory response at birth. These studies will improve our understanding of how the developing fetus and newborn infant regulate sympathetic outflow, increase our knowledge about cardiovascular function early in life and may lead to the development of new therapeutic strategies to prevent morbidity and mortality related to alterations in systemic hemodynamics.