Extended angiotensin converting enzyme inhibition changes the innervation of renal glomerular afferent arterioles

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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 μg/kg/h) for 6 weeks (mean±SEM=634±175×10 3/mm 2 vessel surface, cf. 329±69×10 3/mm 2 vessel surface in untreated rabbits, P=0.05), with the number of neuroeffector junctions remaining the same (124±14 and 164±32×10 3/mm 2 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.