Central Cardiovascular Regulation and Proangiotensin-12

中枢心血管调节和血管紧张素原 12

基本信息

批准号：
8457085
负责人：
HREDAY N. SAPRU
金额：
$ 22.82万
依托单位：
UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-03-05 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8457085
关键词：
AGTR2 gene Abbreviations Agonist American Angiotensin I Angiotensin II Angiotensin II Type 1 Receptor Blockers Angiotensin-Converting Enzyme Inhibitors Angiotensinogen Angiotensins Area Baroreflex Blood Pressure Brain CGP-42112 Calamus angiosperm Cardiopulmonary Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cause of Death Cells Cerebrospinal Fluid Chemoreceptors Congestive Heart Failure Country Cyanides Data Disease Fiber Fluorescein Fluorescein-5-isothiocyanate Future Glutamates Goals Heart Rate Hypertension Hypothalamic structure Intravenous Isothiocyanates Kidney Lumbar spinal cord structure Medial Mediating Microinjections N-Methylaspartate NMDA receptor antagonist Names Nerve Neuraxis Neurons Nucleus solitarius Opioid Receptor Peptide Receptor Peptides Peptidyl-Dipeptidase A Phenylephrine Physiological Play Prevention Rattus Receptor, Angiotensin, Type 1 Reflex action Regulation Renin-Angiotensin System Reporting Right atrial structure Role Site Sodium Sodium Chloride Splanchnic Nerves Stress Structure of area postrema Structure of nucleus infundibularis hypothalami Structure of phrenic nerve Subfornical Organ Techniques Time Tissues Type 2 Angiotensin II Receptor Up-Regulation base design extracellular gamma-Aminobutyric Acid immunoreactivity intraperitoneal nociceptin nucleus ambiguus paraventricular nucleus phenyl biguanide pressure public health relevance receptor response subcutaneous supraoptic nucleus

项目摘要

DESCRIPTION (provided by applicant): A new endogenous angiotensin, angiotensin-(1-12), has been identified recently. In the periphery, angiotensin-(1-12) has been reported to exert its actions via rapid conversion to angiotensin-II. Therefore, angiotensin-(1-12) has been named as "Proangiotensin-12". The presence of Proangiotensin-12 has been reported in various tissues. Upregulation of different components of renin-angiotensin system in various tissues, including the brain, is well established in cardiovascular diseases, such as hypertension, congestive heart failure and stress. Because Proangiotensin-12 may emerge as an important component of the renin-angiotensin system, it is important to investigate the cardiovascular actions of this new angiotensin. Proangiotensin-12 was identified relatively recently (2006). No information is available about the role Proangiotensin-12 in central regulation of cardiovascular function. Our preliminary studies have demonstrated, for the first time, the presence of Proangiotensin-12 immunoreactive neurons and fibers in the hypothalamic paraventricular nucleus (PVN). The PVN is known to project to the medial subnucleus of the nucleus tractus solitarius (mNTS) and the intermediolateral cell column of the thoraco-lumbar spinal cord (IML). The PVN, mNTS and IML play an important role in the central regulation of cardiovascular function. The overall goal of this project is to characterize and understand the mechanism of cardiovascular actions of Proangiotensin-12 in the PVN, mNTS and IML. A multi-disciplinary approach, involving immunohistochemical, physiological, pharmacological and electrophysiological techniques, will be used to accomplish these aims. The results of the proposed studies are likely to provide useful information regarding the role of this new angiotensin in central cardiovascular regulation based on which future studies can be designed in which prevention and treatment of cardiovascular diseases, such as hypertension, can be attempted. The significance of the proposed studies is high considering that over 61 million Americans suffer from some type of cardiovascular disease which is the leading cause of death in this country.

描述（由申请人提供）：最近已经确定了一种新的内源性血管紧张素，血管紧张素（1-12）。在周围，据报道，血管紧张素（1-12）通过快速转化为血管紧张素II发挥作用。因此，血管紧张素（1-12）被命名为“ proangiotensin-12”。在各种组织中已经报道了前血管紧张素-12的存在。包括大脑在内的各种组织中肾素 - 血管紧张素系统的不同成分的上调在心血管疾病（例如高血压，充血性心力衰竭和压力等心血管疾病）中得到了很好的确定。由于proangiotensin-12可能成为肾素 - 血管紧张素系统的重要组成部分，因此研究这种新血管紧张素的心血管作用很重要。 proangiotensin-12最近被发现（2006年）。没有关于在心血管功能中央调节中的角色血管紧张素12的信息。我们的初步研究首次表明，下丘脑旁脑核核（PVN）中的前蛋白-12免疫反应性神经元和纤维存在。已知PVN将投射到核索他叶核（MNT）的内侧亚核和胸胸脊髓（IML）的中间外侧细胞柱。 PVN，MNT和IML在心血管功能的中心调节中起着重要作用。该项目的总体目的是表征和了解PVN，MNTS和IML中Proangiotensin-12的心血管作用的机制。一种涉及免疫组织化学，生理，药理和电生理技术的多学科方法将用于实现这些目标。拟议研究的结果可能会提供有关这种新血管紧张素在中央心血管调节中的作用的有用信息，该研究可以设计为未来的研究，在该研究中，可以尝试预防和治疗心血管疾病，例如高血压。考虑到超过6100万美国人患有某种类型的心血管疾病，这是该国死亡的主要原因，因此提出的研究的重要性很高。