ANF-mediated renal cGMP generation in congestive heart failure.
ANF-mediated renal cGMP generation in congestive heart failure.
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充血性心力衰竭中 ANF 介导的肾脏 cGMP 生成。
DOI：
10.1152/ajprenal.1991.260.4.f562
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
BurnettJr,JC
中科院分区：
文献类型：
--
作者：
Margulies,KB;Heublein,DM;Perrella,MA;BurnettJr,JC
已有研究表明，心钠素（ANF）的生物学作用是通过增加其细胞内第二信使环磷酸鸟苷（cGMP）来介导的。由于cGMP从靶细胞迅速流出后，ANF结合颗粒鸟苷酸环化酶连接的受体，细胞外cGMP可能是一个有用的生物标志物的ANF在体内的作用下的病理生理条件。本研究验证了慢性充血性心力衰竭（CHF）的钠潴留和肾脏ANF抵抗特征与肾脏cGMP对ANF反应减弱相关的假设。我们评估了清醒犬（n = 6）在6天快速心室起搏产生的CHF演变过程中对内源性和外源性ANF的利钠和cGMP反应。同时测量血浆和尿cGMP浓度可确定cGMP的肾脏净生成量，这是肾脏对总尿cGMP排泄的贡献的指标。在早期CHF中，观察到钠排泄和肾cGMP产生增加与血浆ANF增加相关。CHF前给予外源性ANF（10 μ g/kg iv）也可平行增加钠排泄和肾cGMP产生。在起搏6天产生的更晚期CHF中，我们观察到尽管循环ANF进行性增加，但与早期肾cGMP产生增加逆转相关的钠潴留。在慢性CHF中，对外源性ANF的利钠和肾脏cGMP反应同样减弱。这些研究表明：1）肾cGMP产生是ANF肾利钠作用的有用生物标志物; 2）内源性ANF通过增加肾cGMP产生有助于维持早期CHF的钠排泄; 3）晚期CHF中的积极钠潴留和肾ANF抵抗部分与肾cGMP对内源性和外源性ANF的反应减弱有关。
Previous studies have demonstrated that the biological actions of atrial natriuretic factor (ANF) are mediated via increases in its intracellular second messenger guanosine 3',5'-cyclic monophosphate (cGMP). Because cGMP egresses rapidly from target cells after ANF binding to particulate guanylate cyclase-linked receptors, extracellular cGMP may be a useful biological marker for the action of ANF in vivo under pathophysiological conditions. The present studies tested the hypothesis that the avid sodium retention and renal ANF resistance characteristic of chronic congestive heart failure (CHF) are associated with attenuated renal cGMP responses to ANF. We assessed the natriuretic and cGMP responses to endogenous and exogenous ANF during the evolution of CHF produced by 6 days of rapid ventricular pacing in conscious dogs (n = 6). Simultaneous measurement of plasma and urinary cGMP concentrations allowed determination of the net renal generation of cGMP, an indicator of the renal contribution to total urinary cGMP excretion. In early CHF, increased sodium excretion and renal cGMP production were observed in association with increases in plasma ANF. Exogenous ANF administration (10 micrograms/kg iv) before CHF also produced parallel increases in sodium excretion and renal cGMP production. In more advanced CHF produced by 6 days of pacing, we observed avid sodium retention in association with reversal of earlier increases in renal cGMP production despite progressive increases in circulating ANF. Natriuretic and renal cGMP responses to exogenous ANF were similarly attenuated in chronic CHF. These studies suggest that 1) renal cGMP production is a useful biological marker for the renal natriuretic action of ANF; 2) endogenous ANF contributes to the maintenance of sodium excretion in early CHF via increases in renal cGMP production; and 3) the avid sodium retention and renal ANF resistance in advanced CHF are, in part, linked to attenuated renal cGMP responses to endogenous and exogenous ANF.