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：
8259433
负责人：
HREDAY N. SAPRU
金额：
$ 38.61万
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 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8259433
关键词：
AGTR2 gene 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. PUBLIC HEALTH RELEVANCE: Proangiotensin-12 is a newly identified angiotensin. Angiotensins have been implicated in cardiovascular diseases like hypertension. Our preliminary studies have demonstrated the presence of Proangioensin-12 in a brain area which is important in the regulation of cardiovascular function. We have also observed that this peptide elicits diverse cardiovascular responses in different brain areas. In this proposal we will investigate the role of Pronagiotensin-12 in the brain regulation of cardiovascular function. This information is likely to be important in understanding the mechanism of some cardiovascular diseases and provide a basis for devising new treatments for these diseases. The proposed studies are important considering that cardiovascular disease is the leading cause of death in this country.

描述（由申请人提供）：最近已鉴定出一种新的内源性血管紧张素，血管紧张素-(1-12)。据报道，在外周，血管紧张素-(1-12) 通过快速转化为血管紧张素-II 来发挥其作用。因此，血管紧张素-(1-12)被命名为“Proangiotensin-12”。据报道，多种组织中都存在 Proangiotensin-12。包括大脑在内的各种组织中肾素-血管紧张素系统不同成分的上调在心血管疾病（例如高血压、充血性心力衰竭和应激）中已得到证实。由于血管紧张素原 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非常重要。 Proangiotensin-12 是最近才发现的（2006 年）。目前尚无有关血管紧张素原 12 在心血管功能中枢调节中的作用的信息。我们的初步研究首次证明，下丘脑室旁核 (PVN) 中存在原血管紧张素 12 免疫反应性神经元和纤维。众所周知，PVN 投射到孤束核 (mNTS) 的内侧亚核和胸腰脊髓 (IML) 的中间外侧细胞柱。 PVN、mNTS和IML在心血管功能的中枢调节中发挥着重要作用。该项目的总体目标是表征和了解 Proangiotensin-12 在 PVN、mNTS 和 IML 中的心血管作用机制。将采用涉及免疫组织化学、生理学、药理学和电生理学技术的多学科方法来实现这些目标。拟议研究的结果可能会提供有关这种新型血管紧张素在中枢心血管调节中的作用的有用信息，在此基础上可以设计未来的研究，尝试预防和治疗高血压等心血管疾病。考虑到超过 6100 万美国人患有某种类型的心血管疾病，而心血管疾病是该国的主要原因，因此拟议研究的意义非常重大。公共卫生相关性：Proangiotensin-12 是一种新发现的血管紧张素。血管紧张素与高血压等心血管疾病有关。我们的初步研究表明，大脑区域中存在 Proangioensin-12，这对于心血管功能的调节非常重要。我们还观察到这种肽在不同的大脑区域引起不同的心血管反应。在本提案中，我们将研究 Pronagiotensin-12 在大脑心血管功能调节中的作用。这些信息可能对于理解某些心血管疾病的机制很重要，并为设计这些疾病的新疗法提供基础。考虑到心血管疾病是这个国家的主要死亡原因，拟议的研究很重要。