SYMPATHETIC EXCITATORY RESPONSE AT BIRTH

从胎儿到新生儿的转变与许多 通过相互作用的神经实现的生理调节 和荷尔蒙机制。对于定期交货，有令人震惊的 肾素-血管紧张素系统活性的增加和 感同身受的流出。然而，对于早产， 交感兴奋反应缺失，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被证明 改善出生时的心血管反应，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。成人的解剖学、生理学和生化研究 牵涉到下丘脑室旁核(PVN) 在心血管调节中，是前脑输入的主要来源 交感神经系统和联结的一个重要环节 具有中枢自主神经调节的肾素-血管紧张素系统。基座 在这些研究中，我们假设PVN作为一种 出生时交感神经活动的重要调节器 血管紧张素II I型受体表达的发育性变化 并在室旁核内起调节这些交感反应的作用。至 检验这一假设，目前的提议旨在a)阐明 下丘脑室旁核在调节心血管功能中的生理作用 出生时的交感神经功能，b)以确定 中枢自主神经上脑AT1受体的成熟性变化 功能和c)研究PVN和中枢AT1受体 参与糖皮质激素增强交感神经兴奋性 出生时的反应。这些研究将提高我们对 发育中的胎儿和新生儿调节交感神经流出， 在生命的早期增加我们对心血管功能的了解 可能导致开发新的治疗策略来预防 发病率和死亡率与全身血流动力学改变有关。

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.