ATRIAL NATRIURETIC PEPTIDE AND PULMONARY AIR DYNAMICS

这个项目的总体目标是调查 肺组织中的心钠素(ANP)。心钠素是内源性的 心脏因扩张而释放的一种心脏荷尔蒙 众所周知，除了放松血管的平滑肌肉外， 它的利钠和利尿作用。因此，ANP似乎是一种 重要的血压调节器。然而，出现了一个大型 在肺中已经证实了大量的ANP。血浆浓度的增加 在几种肺部病变中也观察到心钠素水平。 条件。然而，人们对心钠素在肺中的功能知之甚少， 特别是关于它放松皮肤平滑肌肉的能力 航空公司。 要检验的假设是：1)ANP在没有 系统性调停者的干预或相互作用或影响 中枢调节的反射，2)呼吸道上皮，特别是 通过其中性内肽酶的作用，改变心钠素的作用 在肺上，ANP直接作用于肺血管的平滑肌细胞。 而不是通过释放其他中间化合物， 4)ANP通过cGMP作为第二信使作用于呼吸道； ANP主要作用于中央呼吸道，而不是外周。 航空公司。 具体目的是为了研究心钠素在心绞痛中的作用和效力 呼吸道反应发生改变的隔离灌流肺 由支气管活性物质引起的。2)研究呼吸道上皮的作用。 尤其是中性内肽酶对心钠素肺作用的影响 机械师。3)研究内皮源性松弛因子的作用 内源性心钠素(EDRF)和环氧合酶抑制剂对心钠素作用的影响 机械师。4)确定ANP是否通过cGMP AS作用于呼吸道 第二个信使。5)确定ANP的作用地点 航空公司。这项拟议的研究具有重要意义，因为 确定心钠素如何调节支气管扩张它可能导致新的 特别是对合并房颤和房颤的情况的治疗 呼吸道功能障碍，如心源性哮喘、充血性心力衰竭和 与慢性阻塞性肺疾病相关的肺心病。

The overall objective of this project is to investigate the role of Atrial Natriuretic Peptide (ANP) in the lung. ANP is an endogenous cardiac hormone which is released by distension of the heart and is known to relax the smooth muscles of the blood vessels in addition to its natriuretic and diuretic properties. Thus, ANP appears to be an important regulator of blood pressure. However, the presence of a large amount of ANP has been demonstrated in the lung. An increase in plasma ANP levels has also been observed in several pulmonary pathological conditions. Yet, little is known about the function of ANP in the lung, particularly regarding its ability to relax the smooth muscles of the airways. The hypotheses to be tested are: 1) ANP works on the airways without the intervention or interaction of systemic mediators or the influence of the centrally mediated reflexes, 2) Airway epithelium, particularly by its action of the neutral endopeptidases, modifies the effect of ANP on the lung, 3) ANP acts directly on the smooth muscle cells of the airways and not through the release of other intermediary compounds, 4) ANP acts on the airways through cGMP as a second messenger, and 5) ANP acts primarily on the central airways rather than on the peripheral airways. The specific aims are l) To study the action and potency of ANP in isolated-perfused lungs where the airway responses have been altered by bronchoactive agents. 2) To study the role of airway epithelium, particularly its neutral endopeptidases, on the action of ANP on lung mechanics. 3) To study the role of endothelial derived relaxing factor (EDRF) and cyclooxygenase inhibitors on the action of ANP on lung mechanics. 4) To determine if ANP acts on the airways through cGMP as the second messenger. 5) To determine the site of action of ANP within the airways. The proposed research is significant in that by establishing how ANP regulates bronchodilation it may lead to new therapies particularly for conditions of combined atrial stretch and airway dysfunction such as cardiac asthma, congestive heart failure and cor pulmonale associated with chronic obstructive pulmonary diseases.