In vivo evidence that cGMP is the second messenger for atrial natriuretic factor.
In vivo evidence that cGMP is the second messenger for atrial natriuretic factor.
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体内证据表明 cGMP 是心房钠尿因子的第二信使。
DOI：
10.1073/pnas.83.20.8015
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发表时间：
1986
影响因子：
11.1
通讯作者：
Cogan,MG
中科院分区：
文献类型：
--
作者：
Huang,CL;Ives,HE;Cogan,MG
cGMP的产生与体外心钠素（ANF）的许多血管和内分泌作用有关。为了研究cGMP作为第二信使在体内ANF肾血流动力学作用中的作用，我们测量了ANF给药后肾小球滤过率（GFR）和体动脉、肾静脉、尿液以及Bowman间隙和近端小管（通过自由流动显微穿刺）中cGMP的浓度。与对照组相比，ANF使GFR增加45%，同时诱导肾小球超滤液（Bowman空间）中cGMP浓度增加5倍以上。体动脉或肾静脉cGMP浓度均无显著增加。因此，Bowman氏间隙cGMP增加的来源不是通过过滤来自血液，而是来自肾小球系膜细胞或上皮细胞，其不与循环直接接触。虽然有少量的肾小管处理cGMP发生沿着肾单位的长度，增加cGMP的生产从肾小球占大多数的10- 12倍的尿cGMP排泄后观察到ANF管理。肾动脉内输注双丁酰cGMP（而非双丁酰cAMP）以剂量依赖性方式（从10 μ M至1000 μ M）增加GFR，其机制与ANF相似-肾小球液压增加。因此，ANF显著刺激肾小球cGMP的产生，这与GFR的显著增加相一致。由于二丁酰cGMP本身能够增加GFR，cGMP可能是体内ANF的第二信使。
cGMP generation has been associated with many of the vascular and endocrine actions of atrial natriuretic factor (ANF) in vitro. To examine the role of cGMP as a second messenger for the renal hemodynamic action of ANF in vivo, we measured glomerular filtration rate (GFR) and cGMP concentration in systemic artery, renal vein, and urine as well as in Bowman's space and end-proximal tubule (by free-flow micropuncture) after administration of ANF. ANF increased GFR by 45% and simultaneously induced a greater than 5-fold increase of cGMP concentration in glomerular ultrafiltrate (Bowman's space) when compared to controls. There was no significant increase in either systemic artery or renal vein cGMP concentration. Thus, the source of increased Bowman's space cGMP is not from the blood via filtration but rather from either glomerular mesangial or epithelial cells, which are not in direct contact with the circulation. Although a small amount of tubular handling of cGMP occurred along the length of the nephron, the augmented cGMP production from the glomerulus accounted for most of the 10- to 12-fold higher urinary cGMP excretion observed after ANF administration. Intrarenal arterial infusion of dibutyryl cGMP, but not dibutyryl cAMP, increased GFR in a dose-dependent fashion (from 10 to 1000 microM) by a mechanism similar to that of ANF--an increase in glomerular hydraulic pressure. Thus, ANF markedly stimulated glomerular production of cGMP, which coincided with a marked increase in GFR. Since dibutyryl cGMP itself was capable of increasing GFR, cGMP is the likely second messenger for ANF in vivo.