Lee S J, Kim S Z, Cui X, Kim S H, Lee K S, Chung Y J, Cho K W
Department of Physiology, Medical School, and Institute for Medical Sciences, Jeonbug National University, Jeonju 561-180, Republic of Korea.
Am J Physiol Heart Circ Physiol. 2000 Jan;278(1):H208-21. doi: 10.1152/ajpheart.2000.278.1.H208.
The purpose of the present experiments was to define the role of C-type natriuretic peptide (CNP) in the regulation of atrial secretion of atrial natriuretic peptide (ANP) and atrial stroke volume. Experiments were performed in perfused beating and nonbeating quiescent atria, single atrial myocytes, and atrial membranes. CNP suppressed in a dose-related fashion the increase in atrial stroke volume and ANP secretion induced by atrial pacing. CNP caused a right shift in the positive relationships between changes in the secretion of ANP and atrial stroke volume or translocation of the extracellular fluid (ECF), which indicates the suppression of atrial myocytic release of ANP into the paracellular space. The effects of CNP on the secretion and contraction were mimicked by 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP). CNP increased cGMP production in the perfused atria, and the effects of CNP on the secretion of ANP and atrial dynamics were accentuated by pretreatment with an inhibitor of cGMP phosphodiesterase, zaprinast. An inhibitor of the biological natriuretic peptide receptor (NPR), HS-142-1, attenuated the effects of CNP. The suppression of ANP secretion by CNP and 8-BrcGMP was abolished by a depletion of extracellular Ca(2+) in nonbeating atria. Natriuretic peptides increased cGMP production in atrial membranes with a rank order of potency of CNP > BNP > ANP, and the effect was inhibited by HS-142-1. CNP and 8-BrcGMP increased intracellular Ca(2+) concentration transients in single atrial myocytes, and mRNAs for CNP and NPR-B were expressed in the rabbit atrium. From these results we conclude that atrial ANP release and stroke volume are controlled by CNP via NPR-B-cGMP mediated signaling, which may in turn act via regulation of intracellular Ca(2+).
本实验的目的是确定C型利钠肽（CNP）在调节心房利钠肽（ANP）分泌和心房每搏输出量中的作用。实验在灌注的跳动和静止的非跳动心房、单个心房肌细胞和心房膜上进行。CNP以剂量相关的方式抑制心房起搏诱导的心房每搏输出量增加和ANP分泌。CNP使ANP分泌变化与心房每搏输出量或细胞外液（ECF）转运之间的正相关关系向右移动，这表明抑制了心房肌细胞将ANP释放到细胞旁间隙。8-溴鸟苷3',5'-环磷酸（8-BrcGMP）模拟了CNP对分泌和收缩的作用。CNP增加了灌注心房中的cGMP生成，并且用cGMP磷酸二酯酶抑制剂扎普司特预处理可增强CNP对ANP分泌和心房动力学的作用。生物利钠肽受体（NPR）抑制剂HS-142-1减弱了CNP的作用。在非跳动心房中，细胞外Ca(2+)耗尽可消除CNP和8-BrcGMP对ANP分泌的抑制作用。利钠肽增加心房膜中的cGMP生成，其效力顺序为CNP>BNP>ANP，并且该作用被HS-142-1抑制。CNP和8-BrcGMP增加单个心房肌细胞中的细胞内Ca(2+)浓度瞬变，并且CNP和NPR-B的mRNA在兔心房中表达。从这些结果我们得出结论，心房ANP释放和每搏输出量由CNP通过NPR-B-cGMP介导的信号传导控制，这反过来可能通过调节细胞内Ca(2+)起作用。
