Biological Actions of Cleaved Atrial Natriuretic Factor (ANF101–105/106–126) in Conscious Sheep
Biological Actions of Cleaved Atrial Natriuretic Factor (ANF101–105/106–126) in Conscious Sheep
复制标题
裂解心房钠尿因子 (ANF101–105/106–126) 在清醒羊中的生物学作用
DOI：
10.1097/00005344-199103000-00008
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发表时间：
1991
影响因子：
3
通讯作者：
A. Richards
中科院分区：
文献类型：
--
作者：
C. Charles;E. Espiner;T. Yandle;V. Cameron;A. Richards
心房利钠因子（ANF）是在Cys 105和Phe 106之间裂解的，是ANF的主要代谢物，并在人血浆中循环。由于这种偏石在体内的作用及其与完整ANF的可能相互作用尚不清楚，我们研究了6只正常绵羊2小时输注大鼠裂解ANF 101 -105 106-126（15 pmol/kg/min）或单独溶媒的生物学效应。输注裂解的ANF使静脉血浆裂解的ANF水平从< 5 pmol/L增加到260 pmol/L，并诱导血浆环GMP的进行性和显著增加（p = 0.025），而不显著影响血浆ANF水平。这些变化与动脉压的小幅（非显著）降低以及心率（HR）和交感神经活动的显著增加相关，随后在输注终止后激活了肾素-血管紧张素-醛固酮（RAA）轴。与ANF本身不同，切割的ANF不是利钠的，也不降低血浆容量或右心房压力。计算的代谢清除率（MCR）（1.47 ± 0.4 L/min）和血浆中裂解ANF的消失率（4.8 ± 0.37 min）与先前报告的绵羊完整ANF的值相似。这些研究表明，切割ANF刺激鸟苷酸环化酶和改变血流动力学和RAA系统在体内。
Atrial natriuretic factor (ANF) cleaved between Cys105 and Phe106 is the primary metaholite of ANF and circulates in human plasma. Because the role of this metaholite in vivo and its possible interaction with intact ANF are unclear, we studied the biologic effects of a 2-h infusion of rat cleaved ANF101–105 106–126 (15 pmol/kg/min) or vehicle alone in six normal sheep. Infusions of cleaved ANF increased venous plasma levels of cleaved ANF from < 5 to 260 pmol/L and induced a progressive and significant increase in plasma cyclic GMP (p = 0.025) without significantly affecting plasma ANF levels. These changes were associated with a small (nonsignificant) decrease in arterial pressure and a significant increase in heart rate (HR) and sympathetic nervous activity and were followed by activation of the renin–angiotensin–aldosterone (RAA) axis after infusions were terminated. Unlike ANF itself, cleaved ANF was not natriuretic and did not reduce plasma volume or right atrial pressure. Calculated metabolic clearance rate (MCR) (1.47 ± 0.4 L/min) and disappearance rate of cleaved ANF from plasma (4.8 ± 0.37 min) were similar to values reported previously for intact ANF in sheep. These studies show that cleaved ANF stimulates guanylate cyclase and alters hemodynamics and the RAA system in vivo.