Luff S E, Young S B, Anderson W P
Department of Physiology, Monash University, Clayton, Victoria, Australia.
J Auton Nerv Syst. 1999 Sep 24;77(2-3):114-24.
Chronic inhibition of the angiotensin I converting enzyme (ACE) with enalapril, results in a phenotypic change of the medial cells of renal afferent arterioles from contractile smooth muscle cells to renin containing epithelioid cells. In normal animals, the density of the innervation of the juxtaglomerular renin containing epithelioid cells is much lower compared to the contractile cells. The effector tissues are known to play an important role in determining the pattern and density of their innervation. In this study, we tested the hypothesis that the density of the innervation of the afferent arteriole smooth muscle cells decreases when they change their phenotype from contractile to renin containing epithelioid cells. The results show that the density of the innervation had significantly increased and the association of the terminals with the smooth muscle cells had changed. There were significantly more varicosities around renal afferent arterioles from rabbits treated with enalapril (10 microg/kg/h) for 6 weeks (mean +/- SEM = 634 +/- 175 x 10(3)/mm2 vessel surface, cf. 329 +/- 69 x 10(3)/mm2 vessel surface in untreated rabbits, P = 0.05), with the number of neuroeffector junctions remaining the same (124 +/- 14 and 164 +/- 32 x 10(3)/mm2 vessel surface) and significantly more non-contacting varicosities (i.e. lying > 100 nm from the medial cells) (74 +/- 5% and 25 +/- 7%, respectively; P = 0.003). Thus, there was no reduction in the innervation of afferent arterioles in which the smooth muscle cells had changed phenotype in response to enalapril treatment as hypothesised. Instead, it would appear that proliferation of the innervation had occurred, with the formation of additional varicosities but these varicosities failed to form neuromuscular junctions. This study has identified a form of neural plasticity in the kidney that has not previously been described.
依那普利对血管紧张素I转换酶（ACE）的慢性抑制作用，会导致肾传入小动脉中层细胞的表型从收缩性平滑肌细胞转变为含肾素的类上皮细胞。在正常动物中，与收缩性细胞相比，含肾素的近球类上皮细胞的神经支配密度要低得多。已知效应组织在决定其神经支配的模式和密度方面发挥着重要作用。在本研究中，我们检验了这样一个假设：当传入小动脉平滑肌细胞从收缩性表型转变为含肾素的类上皮细胞表型时，其神经支配密度会降低。结果显示，神经支配密度显著增加，且神经末梢与平滑肌细胞的关联发生了变化。用依那普利（10微克/千克/小时）处理6周的兔子的肾传入小动脉周围有明显更多的曲张体（平均±标准误 = 634 ± 175×10³/平方毫米血管表面，未处理兔子为329 ± 69×10³/平方毫米血管表面，P = 0.05），神经效应器连接的数量保持不变（分别为124 ± 14和164 ± 32×10³/平方毫米血管表面），非接触性曲张体显著增多（即距离中层细胞大于100纳米）（分别为74 ± 5%和25 ± 7%；P = 0.003）。因此，如假设的那样，在因依那普利处理而平滑肌细胞发生表型改变的传入小动脉中，神经支配并没有减少。相反，似乎发生了神经支配的增殖，形成了额外的曲张体，但这些曲张体未能形成神经肌肉连接。本研究发现了一种此前未被描述过的肾脏神经可塑性形式。
