Geary K M, Hunt M K, Peach M J, Gomez R A, Carey R M
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Endocrinology. 1992 Oct;131(4):1588-94. doi: 10.1210/endo.131.4.1396304.
Angiotensin-converting enzyme inhibition with enalapril increases the number of glomeruli with juxtaglomerular cells and the number of cells in the afferent arteriole that express the renin gene and contain renin. However, renin release from these newly recruited renin-containing cells has not been demonstrated. Sodium depletion also has been shown to increase renal renin messenger RNA levels. The aim of these studies was to determine whether increases in renin secretion are a result of altered numbers of cells synthesizing/releasing renin or a change in the amount of renin release per cell, or both. Adult Wistar-Kyoto rats were treated with enalapril or sodium depleted and single cell renin secretion of enzymatically dispersed renal cortical cells was examined by reverse hemolytic plaque assay. Enalapril treatment increased the number of renin secreting cells by approximately 10-fold (P < 0.05). The newly recruited renin-secreting cells were not responsive to changes in extracellular calcium concentration or the presence of isoproterenol. At physiological (2.5 mM) extracellular calcium concentration, the amount of renin secreted per cell was approximately 2-fold greater (P < 0.05) when cells from enalapril-treated rats were compared to controls and sodium depletion increased both the number of renin-secreting cells and the amount of renin secreted by approximately 35% (P < 0.05). Angiotensin II (AII) inhibited the number of cells secreting renin in cortical cells prepared from enalapril-treated and control rats. In conclusion, angiotensin converting enzyme inhibition increased renin secretion predominantly by recruitment of additional renin-secreting cells and, to a lesser extent, by augmentation of the amount of renin released per cell. In contrast, sodium depletion increased renin secretion equally by both mechanisms. Newly recruited renin-secreting cells were not regulated by the extracellular calcium concentration or beta-adrenergic stimulation. Angiotensin II inhibited renin secretion directly by decreasing the number of individual cells releasing renin through a process which was independent of the extracellular calcium concentration.
依那普利抑制血管紧张素转换酶可增加具有球旁细胞的肾小球数量以及表达肾素基因并含有肾素的入球小动脉中的细胞数量。然而，尚未证实这些新募集的含肾素细胞会释放肾素。钠耗竭也已被证明可增加肾脏肾素信使核糖核酸水平。这些研究的目的是确定肾素分泌增加是由于合成/释放肾素的细胞数量改变，还是每个细胞肾素释放量的变化，或者两者皆有。用依那普利治疗成年Wistar - Kyoto大鼠或使其钠耗竭，并通过反向溶血空斑试验检测酶分散的肾皮质细胞的单细胞肾素分泌情况。依那普利治疗使肾素分泌细胞数量增加了约10倍（P < 0.05）。新募集的肾素分泌细胞对细胞外钙浓度的变化或异丙肾上腺素的存在无反应。在生理（2.5 mM）细胞外钙浓度下，与对照组相比，来自依那普利治疗大鼠的细胞每个细胞分泌的肾素量大约多2倍（P < 0.05），钠耗竭使肾素分泌细胞数量和肾素分泌量均增加了约35%（P < 0.05）。血管紧张素II（AII）抑制了从依那普利治疗和对照大鼠制备的皮质细胞中分泌肾素的细胞数量。总之，血管紧张素转换酶抑制主要通过募集额外的肾素分泌细胞增加肾素分泌，在较小程度上通过增加每个细胞释放的肾素量来实现。相比之下，钠耗竭通过这两种机制同等程度地增加肾素分泌。新募集的肾素分泌细胞不受细胞外钙浓度或β - 肾上腺素能刺激的调节。血管紧张素II通过减少单个释放肾素的细胞数量直接抑制肾素分泌，该过程独立于细胞外钙浓度。
