MECHANISMS OF CARDIAC NATRIURETIC PEPTIDE SYNTHESIS

这项研究提案的目的是研究调节 心钠素(NP)在肺组织中的合成和释放 高血压状态。缺氧性肺动脉高压和肺源性心脏病 慢性肺病患者发病和死亡的主要原因 疾病。越来越多的证据表明，心房利钠肽 心钠素(ANP)和可能的脑自然利尿肽(BNP)在 减轻肺动脉高压和右室的发展 慢性低氧时的肥大。尽管有这些发现，但这些机制 调节NP合成和释放的机制还不是很清楚。我们计划 研究两个可能参与刺激心脏NP的因素 慢性低氧时的产生：心肌拉伸和低氧 紧张。血浆NP水平、心脏NP含量和心脏转录 NPs的翻译将在低氧和非低氧模型中进行测量 肺动脉高压的症状。此外，低氧的独立效应 并将在大鼠的原代细胞培养中研究心肌拉伸 利用低氧细胞培养箱和机械细胞培养的心肌细胞 担架。心脏NPs的产生可能是一种重要的激素 保护右心免受心脏发育不良影响的反馈机制 肺气肿。通过更好地定义如何监管这一机制，我们希望 进一步认识缺氧性肺损伤的病理生理机制 并为NPs如何用于治疗高血压提供了洞察 有肺动脉高压或慢性肺部疾病的患者。

The aim of this research proposal is to study mechanisms that regulate cardiac natriuretic peptide (NP) synthesis and release in pulmonary hypertensive states. Hypoxic pulmonary hypertension and cor pulmonale are major causes of morbidity and mortality in patients with chronic lung diseases. Evidence is accruing to suggest that atrial natriuretic peptide (ANP) and possibly brain naturetic peptide (BNP) play significant roles in mitigating the development of pulmonary hypertension and right ventricular hypertrophy during chronic hypoxia. Despite these findings, the mechanisms that regulate NP synthesis and release are not well understood. We plan to study two factors that are likely to be involved in stimulating cardiac NP production during chronic hypoxia: myocardial stretch and reduced oxygen tension. Plasma NP levels, cardiac NP content, and cardiac transcription and translation of NPs will be measured in hypoxic and non-hypoxic models of pulmonary hypertension. In addition, the independent effects of hypoxia and myocardial stretch will be studied in primary cell cultures of rat cardiocytes using hypoxic cell culture chambers and a mechanical cell stretcher. Cardiac production of NPs may be an important hormonal feedback mechanism to protect the right heart from the development of cor pulmonale. By better defining how this mechanism is regulated, we hope to further the understanding of the pathophysiology of hypoxic pulmonary hypertension and provide insight into how NPs might be used to treat patients with pulmonary hypertension or chronic lung diseases.