Winquist R J
Department of Cardiovascular Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania.
Endocrinol Metab Clin North Am. 1987 Mar;16(1):163-82.
ANP harbors truly remarkable properties in having demonstrable interactions at several key loci of the systems that control blood pressure and extracellular fluid volume. The discovery of ANP by deBold and colleagues succeeded in bringing together neighboring scientists (that is, nephrologists, endocrinologists, cardiologists, and vascularologists), whose research efforts do not often coalesce, in attempts to define the pharmacology and physiology of this peptide. Although we have witnessed a tremendous explosion of interest and work over the past 6 years, several areas of research need to be pursued to obtain these goals. ANP appears to lower blood pressure by reducing either afterload or preload, with the sympathetic state of the individual having an important modulating effect. ANP causes an increased renal secretion of electrolytes, although there is yet to be uniform agreement on the underlying mechanism(s). The depressor and natriuretic effects of ANP act in harmony with an inhibitory effect on the release of aldosterone, renin, and vasopressin. Although this intriguing pharmacologic foundation of ANP has been laid, the physiologic role or importance is still in question. Nonetheless, as we gain further insight into the pharmacology, we stand to advance our knowledge of, and hopefully develop more useful regimens for, cardiovascular and renal pathologic states. As would be expected of an agent that may interact at multiple regulatory sites for control of hemodynamics and fluid volume, differences will most likely exist among species in the pharmacology of ANP, not only as a function of structure-activity relationships but also as a consequence of phylogenic differences in the integration of cardiovascular control.
心钠素具有非凡的特性，在控制血压和细胞外液容量的系统的几个关键位点上具有可证实的相互作用。德博尔德及其同事发现的心钠素成功地将相邻领域的科学家（即肾病学家、内分泌学家、心脏病学家和血管学家）聚集在一起，他们的研究工作通常不会合并，而是试图确定这种肽的药理学和生理学特性。尽管在过去6年里我们见证了对其兴趣和研究工作的巨大爆发，但仍有几个研究领域需要探索以实现这些目标。心钠素似乎通过降低后负荷或前负荷来降低血压，个体的交感神经状态具有重要的调节作用。心钠素可导致肾脏电解质分泌增加，尽管其潜在机制尚未达成一致意见。心钠素的降压和利钠作用与对醛固酮、肾素和血管加压素释放的抑制作用协同发挥作用。尽管心钠素有趣的药理学基础已经奠定，但其生理作用或重要性仍存在疑问。尽管如此，随着我们对其药理学有更深入的了解，我们有望增进对心血管和肾脏病理状态的认识，并有望开发出更有效的治疗方案。正如一种可能在多个调节位点相互作用以控制血流动力学和液体容量的药物所预期的那样，心钠素的药理学在不同物种之间很可能存在差异，这不仅是结构 - 活性关系的函数，也是心血管控制整合中系统发育差异的结果。
