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

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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.