Significance and clinical application of atrial natriuretic polypeptide as hormone and neuropeptide

继Matsuo等和de Bold等分离出心房钠尿肽（ANP）后，我们制备了ANP的特异性抗体，并应用放射免疫分析和组织化学方法，阐明了ANP作为一种调节体液和血压的激素的生理和病理生理意义。此后，我们研制了几种抗ANP不同表位的单克隆抗体，并建立了ANP mRNA的北方印迹杂交分析方法。利用这些工具，我们研究了心钠素在心脏中的生物合成、加工和分泌，并阐明了心脏作为内分泌器官的一些特征。我们已经证明了ANP基因在高血压和充血性心力衰竭中的表达增强及其在这些心血管疾病的病理生理学中的意义。因此，我们提出了ANP基因在患病心脏中的增强表达是心脏的自我代偿反应，并证明了ANP给药在临床上可用于治疗心血管疾病。作为诊断工具，我们建立了高灵敏度的ANP酶免疫测定法，其灵敏度比放射免疫测定法高100倍。我们还证明了ANP存在于中枢神经系统，特别是在前腹侧第三脑室区，这是已知的体液和血压的中枢控制的重要区域，心钠素作为一种神经肽参与体液和心血管功能的中枢调节。因此，ANP作为一种激素和神经肽参与体液和血压的调节，在此基础上，本实验室开展了ANP的临床应用研究。

Following the isolation of atrial natriuretic polypeptide (ANP) by Matsuo et al and by de Bold et al, we prepared specific antibody for ANP and using radioimmunoassay and histochemistry, we have elucidated the physiological and pathophysiological significance of ANP as a hormone implicated in the control of body fluid and blood pressure. Since then, we have developed several monoclonal antibodies against different epitopes of ANP and also set up Northern blot hybridization analysis for ANPmRNA. Using these tools, we have investigated the biosynthesis, processing and secretion of ANP in the heart and have elucidated some characteristics of the heart as an endocrine organ. We have demonstrated the augmented expression of the ANP gene in hypertension and congestive heart failure and its significance in pathophysiology of these cardiovascular disorders. So, we have proposed that the augmented expression of the ANP gene in the diseased heart is self-compensatory response of the heart, and demonstrated that ANP administration is clinically useful for treatment of cardio-vascular disorders. As diagnostic tools, we have established highly sensitive enzyme immunoassay for ANP of which sensitivity is 100 times higher than that of radioimmunoassay for ANP.We also demonstrated that ANP is present in the central nervous system, especially in the anteroventral third ventricular region which is known to be an important area for the central control of body fluid and blood pressure, and that ANP acts as a neuropeptide in the central regulation of body fluid and cardiovascular function. Thus, ANP is implicated in the control of body fluid and blood pressure as a hormone and a neuropeptide.Based on these basic studies on ANP, our clinical application of ANP is in progress in our laboratory.