LUNG VASCULAR /AIRWAY EFFECTS OF ADRENOMEDULLIN

肾上腺髓质素对肺血管/气道的影响

• 批准号: 6349109
• 负责人: MUKUL R BANERJEE
• 金额: $ 11.77万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6349109
• 关键词: atrial natriuretic peptide; bronchomotion; endopeptidases; enzyme activity; laboratory rat; lung; muscle relaxing factor; nitric oxide; peptide hormone; pulmonary circulation; respiratory airflow disorder; respiratory epithelium; respiratory function; respiratory muscles; second messengers; vascular smooth muscle; vasodilators

The overall objective of this project is to investigate the role of Adrenomedullin (ADM) in the lung. ADM is an endogenous peptide which is ubiquitously distributed in human tissues including plasma and it increases during physical exercise. ADM relaxes the smooth muscles of the blood vessels. The vasorelaxant effect is more potent in pulmonary artery than in the aorta. ADM appears to play a role in the regulation of systemic and pulmonary arterial blood pressure. Atrial Natriuretic Peptide (ANP) increases the release of ADM and the hemodynamic effects of ANP may be partially due to ADM. ADM-mRNA is highly expressed in the basal cells of the airway epithelium and Type II pneumocytes in the lung in addition to the cardiovascular tissue, kidney and adrenal medulla. It is possible that ADM is synthesized in the lung tissue and is released into the peripheral blood and airway lumen. An increase in plasma ADM levels has been observed in congestive heart failure and in pulmonary disorders. Yet, the role of ADM in the lung under physiologic and pathophysiologic conditions is not known, in particular the ability of ADM to relax the smooth muscles of the airways. The specific aims are: 1) To study the action and potency of ADM in isolated-perfused lungs where airway responses have been altered by bronchoactive agents. 2) To study the role of airway epithelium, particularly its neutral endopeptidases, on the action of ADM on lung mechanics. 3) To study the role of endothelial derived relaxing factor (EDRF) and cyclooxygenase inhibitors on the action of ADM on lung mechanics. 4) To determine if ADM acts on the airways through cAMP as the second messenger. 5) To determine the site of action of ADM within the airways. The proposed research is significant in that by establishing how ADM regulates bronchodilation it may lead to new therapies in pulmonary diseases characterized by airway obstruction.

该项目的总体目标是研究肾上腺髓质素 (ADM) 在肺部的作用。 ADM是一种内源性肽，广泛分布于血浆等人体组织中，并在体育锻炼时增加。 ADM 可以放松血管平滑肌。血管舒张作用在肺动脉中比在主动脉中更有效。 ADM 似乎在调节全身动脉血压和肺动脉血压中发挥作用。心钠素 (ANP) 增加 ADM 的释放，ANP 的血流动力学效应可能部分归因于 ADM。除了心血管组织、肾和肾上腺髓质外，ADM-mRNA 在气道上皮基底细胞和肺 II 型肺细胞中高表达。 ADM 可能在肺组织中合成并释放到外周血和气道腔中。在充血性心力衰竭和肺部疾病中观察到血浆 ADM 水平升高。然而，ADM 在生理和病理生理条件下在肺中的作用尚不清楚，特别是 ADM 放松气道平滑肌的能力。具体目标是： 1) 研究 ADM 在离体灌注肺中的作用和效力，其中气道反应已被支气管活性药物改变。 2) 研究气道上皮，特别是其中性肽链内切酶对ADM对肺力学作用的影响。 3)研究内皮衍生舒张因子(EDRF)和环氧合酶抑制剂对ADM对肺力学作用的影响。 4) 确定ADM是否通过cAMP作为第二信使作用于气道。 5) 确定ADM在气道内的作用位点。拟议的研究意义重大，因为通过确定 ADM 如何调节支气管扩张，可能会带来以气道阻塞为特征的肺部疾病的新疗法。