Bähr V, Sander-Bähr C, Ardevol R, Tuchelt H, Beland B, Oelkers W
Department of Internal Medicine, Klinikum Steglitz, Freie Universität Berlin, Germany.
J Steroid Biochem Mol Biol. 1993 Apr;45(1-3):173-8. doi: 10.1016/0960-0760(93)90138-m.
We investigated the effect of high physiological plasma levels of human varies; is directly proportional to atrial natriuretic factor (ANF) on renin and aldosterone secretion in normal sodium deplete men. In short term infusion studies (2 or 8 h duration), ANF plasma levels as observed after sodium loading (50-70 pg/ml) lowered basal renin (PRA) and aldosterone, but had only a marginal effect on angiotensin II-stimulated aldosterone secretion. Preliminary results of a study with long term infusion (6 days) of ANF during a period of dietary sodium depletion argue against a significant tonic inhibitory effect of ANF on the renin-aldosterone system in the preceding period of sodium repletion: the plasma aldosterone response to sodium depletion was similar with and without ANF infusion. The second messenger of ANF for the direct inhibition of aldosterone secretion from zona glomerulosa cells is still unknown. To test the hypothesis, that cGMP is the second messenger of ANF, we produced a rise in intracellular cGMP in rat and rabbit zona glomerulosa cells using the unspecific phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) and the more cGMP specific phosphodiesterase specific inhibitor M + B2948 (Zaprinast). Both inhibitors simulated the action of ANF in suppressing steroid secretion and elevating cGMP levels. The results are compatible with the view that cGMP is of importance as a second messenger for ANF in adrenal zona glomerulosa cells. Selective inhibition of phosphodiesterases in combination with endopeptidase inhibition may be an interesting principle to enhance the action of endogenous and exogenous ANF.
我们研究了正常人在钠缺乏状态下，生理水平的人心房利钠因子（ANF）对肾素和醛固酮分泌的影响。在短期输注研究（持续2或8小时）中，钠负荷后观察到的ANF血浆水平（50 - 70 pg/ml）降低了基础肾素（PRA）和醛固酮水平，但对血管紧张素II刺激的醛固酮分泌仅有轻微影响。在饮食性钠缺乏期间长期输注ANF（6天）的一项研究的初步结果表明，在先前的钠补充期，ANF对肾素 - 醛固酮系统没有显著的持续性抑制作用：无论是否输注ANF，血浆醛固酮对钠缺乏的反应相似。ANF直接抑制肾小球带细胞醛固酮分泌的第二信使仍不清楚。为了验证cGMP是ANF的第二信使这一假设，我们使用非特异性磷酸二酯酶抑制剂3 - 异丁基 - 1 - 甲基黄嘌呤（IBMX）和更具cGMP特异性的磷酸二酯酶特异性抑制剂M + B2948（扎普司特），使大鼠和兔肾小球带细胞内的cGMP升高。两种抑制剂都模拟了ANF抑制类固醇分泌和升高cGMP水平的作用。这些结果与cGMP作为ANF在肾上腺肾小球带细胞中的第二信使具有重要作用这一观点相符。选择性抑制磷酸二酯酶并结合内肽酶抑制可能是增强内源性和外源性ANF作用的一个有趣原则。
