Henrich W L, Needleman P, Campbell W B
Life Sci. 1986 Sep 15;39(11):993-1001. doi: 10.1016/0024-3205(86)90288-2.
The ability of atriopeptin III (AP) to directly inhibit renal renin release has not been resolved. This issue was examined in a series of experiments performed in a system of rat renal cortical slices (dry weight 1.91 mg) in which the goal was to explore the effects of AP on renin release induced by cyclic AMP (cAMP)-coupled stimuli or by agents which are believed to decrease intracellular calcium (Cai). Concentration response relationships were initially established for all test agents. The cAMP stimuli utilized were isoproterenol (10(-5) M), forskolin (10(-5) M), and dibutyryl cAMP (3 X 10(-4) M); each of these agents produced a significant increase in renin release in the system (with isoproterenol a 59% increase, with forskolin 37%, and with dibutyryl cAMP 52%). The addition of AP (2.09 X 10(-8) M, a minimum inhibitory concentration derived from preliminary studies) significantly blunted these increases; in the case of the dibutyryl cAMP-stimulated renin release, the inhibition was partial as a significant 25% increase in renin occurred in the presence of AP. The addition of the calcium channel blocking agent diltiazem (10(-4) M) resulted in a significant increase in renin release (364 to 567 ng X mg-1, p less than .05) which was not blocked by the addition of AP. Similarly, TMB-8 (0.6 X 10(-4) M), another agent thought to lower Cai, also resulted in increased renin release (455 to 810 ng X mg-1), p less than .01) which was also unaffected by the addition of the AP. In summary, these results show that AP is capable of partially inhibiting renin release in vitro, particularly renin release coupled to cAMP action. In contrast, renin release induced by a decline in Cai appears to be unaffected by the addition of AP.
心房肽III（AP）直接抑制肾脏肾素释放的能力尚未明确。在一系列以大鼠肾皮质切片系统（干重1.91毫克）进行的实验中对该问题进行了研究，其目的是探究AP对由环磷酸腺苷（cAMP）偶联刺激或被认为可降低细胞内钙（Cai）的试剂所诱导的肾素释放的影响。首先为所有测试试剂建立浓度反应关系。所使用的cAMP刺激剂为异丙肾上腺素（10⁻⁵ M）、福斯可林（10⁻⁵ M）和二丁酰cAMP（3×10⁻⁴ M）；这些试剂中的每一种在该系统中均使肾素释放显著增加（异丙肾上腺素使肾素释放增加59%，福斯可林增加37%，二丁酰cAMP增加52%）。添加AP（2.09×10⁻⁸ M，这是根据初步研究得出的最小抑制浓度）显著减弱了这些增加；就二丁酰cAMP刺激的肾素释放而言，抑制是部分性的，因为在有AP存在的情况下肾素仍有显著的25%的增加。添加钙通道阻滞剂地尔硫䓬（10⁻⁴ M）导致肾素释放显著增加（364至567纳克×毫克⁻¹，p<0.05），而添加AP并未阻断这种增加。同样，另一种被认为可降低Cai的试剂TMB - 8（0.6×10⁻⁴ M）也导致肾素释放增加（455至810纳克×毫克⁻¹，p<0.01），添加AP对此也无影响。总之，这些结果表明AP能够在体外部分抑制肾素释放，特别是与cAMP作用相关的肾素释放。相比之下，由Cai下降所诱导的肾素释放似乎不受添加AP的影响。
