Prenatal Events-Postnatal Consequences

产前事件-产后后果

• 批准号: 7683209
• 负责人: JAMES C. ROSE
• 金额: $ 126.85万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-20 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7683209
• 关键词: Prenatal; Events; Postnatal; Consequences

DESCRIPTION (provided by the applicant): The primary goal of this program project application is to investigate the long-term effects of antenatal exposure to synthetic glucocorticoids on renal functional and blood pressure postnatally. This topic has major significance today because of the widespread clinical use of synthetic glucocorticoids in the perinatal period to enhance lung maturation. The proposed studies encompass three projects in the same, widely used animal model (the sheep at different stages of development) to examine specific systems and mechanisms mediating the effects of antenatal steroid treatment on aspects of kidney development and function, the neural control of the cardiovascular system and blood pressure. They are coupled with a clinical project to document in children between 10-16 years of age, the effects of glucocorticoid exposure on blood pressure, blood pressure responsivity and indices of renal function. Specifically, Project 1 examines the impact of prenatal steroid exposure on the intra-renal renin-angiotensin system, renal function in vivo and blood pressure at different stages of development. Project 2 focuses on the effects of prenatal steroid exposure on sodium handling by the kidney using both in vitro and in vivo approaches. Project 3 establishes the impact of antenatal glucocorticoids on the brain renin angiotensin system, baroreceptor function and the regulation of sympathetic outflow. Finally, Project 4 establishes, in a well-defined patient population, the impact of prenatal steroid exposure on blood pressure, the responsiveness of blood pressure to stimulation and on indices of renal functional in children and how this impact is modulated by factors such as growth and fitness. Thus, all the animal projects have a high level of scientific integration and the results of the clinical project will provide a high level of relevance for the work in the animal model. The data obtained will improve our understanding of the consequences of the use of glucocorticoids antenatally and may help to identify a population of children at risk for the development of high blood pressure as adults. This outcome would obviously serve as a stimulus for the development of monitoring and early intervention strategies to be used in children exposed to glucocorticoids prior to birth. Thus, a long-term benefit of the proposed studies may be to reduce the overall morbidity associated with elevations in blood pressure in such a population.

描述（由申请人提供）：该计划项目应用的主要目标是研究产前对合成糖皮质激素对肾脏功能和血压的长期影响。今天，该主题具有重要意义，因为在围产期期间，合成糖皮质激素的广泛临床使用以增强肺部成熟。拟议的研究涵盖了相同的，广泛使用的动物模型（不同发育阶段的绵羊）的三个项目，以检查介导产前类固醇治疗对肾脏发育和功能方面的影响的特定系统和机制，心血管系统的神经控制和血压。它们与一个临床项目相结合，可以记录10-16岁儿童，糖皮质激素暴露对血压，血压反应性和肾功能指数的影响。具体而言，项目1检查了产前类固醇暴露对肾上腺内肾素 - 血管紧张素系统，体内肾功能和血压在不同发育阶段的影响。项目2侧重于使用体外和体内方法使用产前类固醇暴露对肾脏处理的影响。项目3建立了产前糖皮质激素对脑肾素血管紧张素系统，压力感受器功能以及交感神经流出的调节的影响。最后，项目4在定义明确的患者人群中建立了产前类固醇暴露对血压的影响，血压对刺激的反应性以及儿童肾功能指标以及这种影响如何受到成长和适应性等因素的调节。因此，所有动物项目都具有很高的科学整合，临床项目的结果将为动物模型的工作提供很高的相关性。获得的数据将提高我们对糖皮质激素使用的后果的理解，并可能有助于确定有可能发展高血压的儿童人群。这种结果显然将是开发监测和早期干预策略的刺激，并在出生前暴露于糖皮质激素的儿童中使用。因此，提出的研究的长期益处可能是减少与此类人群血压升高有关的总体发病率。