MECHANISMS OF CARDIAC NATRIURETIC PEPTIDE SYNTHESIS

这项研究计划的目的是研究调节 心脏利钠肽（NP）的合成和释放 高血压状态 低血压性肺动脉高压和肺心病是 慢性肺疾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钠素 (ANP)脑钠肽（BNP）可能在其中发挥重要作用 减轻肺动脉高压和右心室的发展 慢性缺氧时的肥大。尽管有这些发现， 调节NP合成和释放的分子机制尚不清楚。我们计划 研究两个可能参与刺激心脏NP的因素 慢性缺氧期间的产生：心肌牵张和氧减少 张力血浆NP水平、心脏NP含量和心脏转录 将在缺氧和非缺氧模型中测量NPs的翻译 肺动脉高压此外，缺氧的独立影响 在原代培养的大鼠心肌细胞中， 使用低氧细胞培养室和机械细胞的心肌细胞 担架 心脏产生的NPs可能是一种重要的激素 保护右心免受心脏病发展的反馈机制 肺结核。通过更好地定义如何监管这一机制，我们希望 进一步了解缺氧性肺动脉高压的病理生理机制， 高血压，并提供如何NP可能用于治疗的见解 肺动脉高压或慢性肺部疾病患者。

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.