Studies on mechanisms of atrial natriuretic peptide secretion

为了探讨心房利钠肽(ANP)的病理生理作用，我们在不同的实验和临床条件下观察了心房压与血浆ANP浓度的关系，以及ANP对心血管和肾脏疾病患者的影响。大鼠血容量扩张和高渗刺激均使血浆ANP浓度升高。血浆ANP浓度的增加与尿钠排泄和心房压的增加有关。左房气囊扩张和右房快速起搏也增加了ANP的分泌和房压。充血性心力衰竭患者血浆ANP浓度随着心力衰竭症状严重程度指数的增加而升高，血浆ANP浓度与心房压呈显著正相关。阵发性房性心动过速患者血浆ANP水平也明显升高。这些结果表明，心房收缩似乎是ANP分泌的最重要刺激。除心脏病外，各种水肿性疾病和高血压也表现出血浆ANP浓度升高。当ANP被注入这些疾病的患者时，ANP具有强大的血管舒张剂(降压剂)、利钠和抑制醛固酮的作用，提示这种多肽可能用于治疗。血浆和尿液cGMP浓度明显升高。这些发现支持cGMP作为ANP的细胞内第二信使。此外，基础血浆cGMP水平也与血浆ANP浓度密切相关。提示血浆cGMP可作为内源性ANP活性的良好标志物。因此，ANP通过直接或间接的房性扩张而分泌，可能在血压和体液容量调节中起着病理生理学作用。

To explore the pathophysiological roles of atrial natriuretic peptide (ANP), we examined the relationship between atrial pressure and plasma concentration of ANP in various experimental and clinical conditions and the effects of ANP infusion into patients with cardiovascular and renal diseases. Both volume expansion and hyperosmotic stimulus in rats increased plasma concentration of ANP. This increase in the plasma ANP concentration was associated with increases in urinary Na excretion and atrial pressure. Left atrial ballooning and right atrial rapid pacing also increased ANP secretion and atrial pressure. In patients with congestive heart failure, plasma ANP concentration increased with the severity index of the heart failure symptoms, resulting in a significant positive correlation of plasma ANP concentration with atrial pressure. Plasma ANP level was also elevated during paroxysmal atrial tachycardia. These results suggest that atrial strtch seems to be the most important stimulus for ANP secretion. In addition to heart diseases, various kinds of edematous disorders and hypertension also showed increased plasma ANP concentration. When ANP was infused into patients with these diseases, ANP exerted potent vasorelaxant (depressor), natriuretic and alsdosterone suppressive effects, suggesting the possible therapeutic use of this peptide. ANP infusion markedly elevated plasma and urinary cGMP concentrations. These findings support that cGMP acts as an intracellular second messenger of ANP. Furthermore, basal plasma cGMP level was also closely correlated with the plasma concentration of ANP. This suggests that plasma cGMP seems to be a good marker of endogenous ANP activity. Thus, ANP, which secretes through direct or indirect atrial extention, may play a pathophysiological role in blood pressure and body fluid volume regulation.