CARDIOVASCULAR ACTIONS OF MELANOCORTINS

黑皮质素的心血管作用

基本信息

批准号：
7369896
负责人：
HREDAY N. SAPRU
金额：
$ 33.17万
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 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7369896
关键词：
Address Agonist American Animals Area Attenuated Baroreflex Bilateral Bradycardia Brain region Cardiac Cardiopulmonary Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cause of Death Cell Nucleus Cells Chemicals Chemoreceptors Condition Conscious Corticotropin Country Disruption Dorsal Eating Electric Stimulation Endocrine Excitatory Amino Acid Antagonists Excitatory Amino Acids Experimental Designs Family Feeding behaviors GABA Receptor GABA-B Receptor Genes Glutamate Receptor Glutamates Glycine Glycine Receptors Goals Heart Heart Rate Hyperphagia Hypertension Hypotension Hypothalamic structure Investigation Ipsilateral Laboratories Lateral Hypothalamic Area Lead Left Link Mediating Melanocortin 3 Receptor Melanocortin 4 Receptor Methods Microinjections Myocardial Neuraxis Neurons Neurotransmitter Receptor Nucleus solitarius Obesity Pathway interactions Peptides Pharmaceutical Preparations Pituitary Gland Pressoreceptors Principal Investigator Pro-Opiomelanocortin Probability Publishing Rattus Reflex action Regulation Reporting Reticular Formation Risk Factors Role SHU 9119 Side Specificity Spinal Staining method Stains Stress Structure Structure of nucleus infundibularis hypothalami Tachycardia Techniques Testing Treatment Protocols Vagotomy Vagus nerve structure alpha-Melanocyte stimulating hormone base beta-Endorphin beta-MSH biological adaptation to stress direct application experience extracellular gamma-Aminobutyric Acid gamma-MSH melanocortin receptor melanocyte novel nucleus ambiguus programs receptor relating to nervous system research study response voltage

项目摘要

Over 61 million Americans have some type of cardiovascular disease that is the leading cause of death in this country. Obesity and stress are two high risk factors for cardiovascular disease, especially hypertension. The melanocortins consist of a family of peptides derived from the common precursor pro-opiomelanocortin. These peptides include alpha-, beta-, and gamma-melanocyte stimulating and adrenocorticotropic hormones. Melanocortins have been implicated in feeding behavior, obesity and stress responses. For example, disruption of melanocortin containing neurons produces over eating and obesity. Mild stress has been reported to elicit over eating that can lead to obesity. In addition, melanocortin levels are elevated in stressful situations. These observations suggest that there may be a link between melanocortins, obesity, stress and cardiovascular disease. A prerequisite for understanding the role of melanocortins in cardiovascular function during obesity and stress is a clear understanding of the role of these peptides in the central cardiovascular regulation in normal conditions. The goal of the present project is to investigate the mechanism of cardiovascular actions of melanocortins in the nucleus tractus solitarius, caudal ventrolateral medullary depressor area, rostral ventrolateral medullary pressor area, the nucleus ambiguus, and the intermediolateral cell column of the thoraco-lumbar cord. These areas of the central nervous system are known to be involved in the regulation of cardiovascular function. Dense neuronal networks containing melanocortins have been identified in these regions. The hypothesis central to this project is that melanocortins excite neurons located in the medullo-spinal regions involved in cardiovascular regulation. The hypothesis is based on our preliminary results and published reports in which electrophysiological studies have shown excitation of neurons in specific regions of the brain. In each of the abovementioned regions, pharmacological and electrophysiological techniques will be used to investigate the mechanism of action of melanocortins. The information generated from this project will eventually be helpful in understanding the mechanisms connecting melanocortins, obesity, stress and cardiovascular disease. Furthermore, this information will help in developing novel and rational regimens of treatment for cardiovascular disease.

超过6100万美国人患有某种类型的心血管疾病，这是该国的主要死亡原因。肥胖和压力是心血管疾病，尤其是高血压的两个高风险因素。黑色素皮质蛋白由源自普通前体促蛋白酶皮质素的肽家族组成。这些肽包括α-，β-和γ-甲状腺细胞刺激和肾上腺皮质激素激素。黑色皮质素与喂养行为，肥胖和压力反应有关。例如，含有神经元的黑色皮质素的破坏会产生饮食和肥胖症。据报道，轻度压力会引起饮食，这可能导致肥胖。另外，在压力的情况下，黑色皮质素水平升高。这些观察结果表明，黑色素皮质，肥胖，压力和心血管疾病之间可能存在联系。了解黑素皮质素在肥胖和压力过程中心血管功能中的作用的先决条件是对这些肽在正常条件下中央心血管调节中的作用的明确理解。本项目的目的是研究黑色素皮质素在核索他叶核中的心血管作用机理，尾腔外侧髓质抑制剂区域，thostral腹侧髓外侧压力区域，Ambiguus核和胸腔宽头胸膜中间型细胞柱。已知中枢神经系统的这些区域与心血管功能的调节有关。在这些区域已经确定了含有黑色皮质素的密集神经元网络。该项目的中心假设是，黑色素皮质激发了位于涉及心血管调节的髓质区域的神经元。该假设是基于我们的初步结果和发表的报告，在该报告中，电生理学研究表明了大脑特定区域的神经元激发。在每个上述区域中，将使用药理学和电生理技术来研究黑色皮质素的作用机理。该项目产生的信息最终将有助于理解连接黑色皮质素，肥胖，压力和心血管疾病的机制。此外，这些信息将有助于开发心血管疾病的新颖和理性治疗方案。