CARDIOVASCULAR ACTIONS OF MELANOCORTINS

黑皮质素的心血管作用

• 批准号: 6865423
• 负责人: HREDAY N. SAPRU
• 金额: $ 34.99万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-05 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6865423
• 关键词: GABA receptor; adrenocorticotropic hormone; baroreceptors; brain mapping; cardiovascular function; chemoreceptors; electrophysiology; hormone receptor; laboratory rat; medulla oblongata; melanocyte stimulating hormone; microinjections; neuroregulation; proopiomelanocortin; vagus nerve

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，这是该国的主要原因。肥胖和压力是心血管疾病尤其是高血压的两个高危因素。黑皮质素由衍生自常见前体阿片黑皮质素原的肽家族组成。这些肽包括α-、β-和γ-黑素细胞刺激激素和促肾上腺皮质激素。黑皮质素与进食行为、肥胖和压力反应有关。例如，含有黑皮质素的神经元的破坏会导致暴饮暴食和肥胖。据报道，轻微的压力会引起暴饮暴食，从而导致肥胖。此外，在压力情况下，黑皮质素水平会升高。这些观察结果表明，黑皮质素、肥胖、压力和心血管疾病之间可能存在联系。了解黑皮质素在肥胖和压力期间心血管功能中的作用的先决条件是清楚地了解这些肽在正常情况下中央心血管调节中的作用。本项目的目标是研究黑皮质素在孤束核、尾侧腹外侧延髓降压区、头侧腹外侧延髓升压区、疑核和胸腰索中间外侧细胞柱中的心血管作用机制。已知中枢神经系统的这些区域参与心血管功能的调节。在这些区域已发现含有黑皮质素的密集神经元网络。该项目的核心假设是黑皮质素会兴奋位于参与心血管调节的髓脊髓区域的神经元。该假设基于我们的初步结果和已发表的报告，其中电生理学研究表明大脑特定区域的神经元受到兴奋。在上述每个区域中，将使用药理学和电生理学技术来研究黑皮质素的作用机制。该项目产生的信息最终将有助于理解黑皮质素、肥胖、压力和心血管疾病之间的联系机制。此外，这些信息将有助于开发新颖且合理的心血管疾病治疗方案。