Eisen V, Munday M R, Slater J D
Biochem Pharmacol. 1987 Jul 15;36(14):2331-5. doi: 10.1016/0006-2952(87)90599-5.
The interplay of juxtaglomerular (jg) calcium fluxes and exposure to AII in the regulation of jg renin secretion, was examined in vivo. An inhibitor of angiotensin I converting enzyme (captopril), a blocker of calcium channels (verapamil) and AII amide were infused, singly or in combination, into the ear vein of conscious rabbits. The effects on arterial pressure, and on levels of active and inactive plasma renin were monitored. Captopril (50 micrograms X min-1 X kg-1) produced a greater percentage increase in renin secretion than did verapamil (20 micrograms X min-1 X kg-1), whilst the percentage fall in arterial pressure was similar. AII amide counteracted more effectively the actions of captopril than those of verapamil. When captopril was infused first, addition of verapamil did not enhance renin secretion (P greater than 0.2). When verapamil was infused first, addition of captopril greatly enhance renin secretion (P less than 0.01). However, when captopril was infused first, and its actions then suppressed by AII amide, addition of verapamil led to extremely high rates of renin secretion. The findings suggest the following: the short loop negative feedback plays in vivo an important role in the rapid modulation of jg renin secretion and the action of AII may involve up- and down-regulation at the receptor and/or post-receptor level; infused agents have rapid access to the critical sites of jg cells; exposure to raised concentrations to AII not only reduces the effectiveness of AII, but also enhances jg secretory responses to lack of AII, as well as to calcium channel blockade. Thus, at least some of the jg calcium channels appear to respond both to AII and to blockers; extreme changes in the levels of active renin are possible without changes of inactive renin levels. Secretion of the latter may be under separate control, or its secretion rate parallelled by the rate of its activation.
在体内研究了球旁（JG）钙通量与血管紧张素II（AII）暴露在调节JG肾素分泌中的相互作用。将血管紧张素I转换酶抑制剂（卡托普利）、钙通道阻滞剂（维拉帕米）和AII酰胺单独或联合注入清醒家兔的耳静脉。监测对动脉血压以及活性和非活性血浆肾素水平的影响。卡托普利（50微克·分钟-1·千克-1）引起的肾素分泌百分比增加比维拉帕米（20微克·分钟-1·千克-1）更大，而动脉血压的下降百分比相似。AII酰胺比维拉帕米更有效地抵消卡托普利的作用。当先注入卡托普利时，添加维拉帕米不会增强肾素分泌（P＞0.2）。当先注入维拉帕米时，添加卡托普利会大大增强肾素分泌（P＜0.01）。然而，当先注入卡托普利，然后其作用被AII酰胺抑制时，添加维拉帕米会导致极高的肾素分泌率。这些发现表明：短环负反馈在体内对JG肾素分泌的快速调节中起重要作用，AII的作用可能涉及受体和/或受体后水平的上调和下调；注入的药物能迅速到达JG细胞的关键部位；暴露于升高浓度的AII不仅会降低AII的有效性，还会增强JG对AII缺乏以及钙通道阻滞的分泌反应。因此，至少一些JG钙通道似乎对AII和阻滞剂都有反应；活性肾素水平可能发生极端变化而不伴有非活性肾素水平的变化。后者的分泌可能受单独控制，或者其分泌速率与其激活速率平行。
