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

Chronic inhibition of the angiotensin I converting enzyme (ACE) with enalap ril, results in a phenotypic change of the medial cells of renal afferent a rterioles from contractile smooth muscle cells to renin containing epitheli oid cells. In normal animals, the density of the innervation of the juxtagl omerular renin containing epithelioid cells is much lower compared to the c ontractile 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 afferen t arteriole smooth muscle cells decreases when they change their phenotype from contractile to renin containing epithelioid cells. The results show th at the density of the innervation had significantly increased and the assoc iation of the terminals with the smooth muscle cells had changed. There wer e significantly more varicosities around renal afferent arterioles from rab bits treated with enalapril(10 mu g/kg/h) for 6 weeks (mean +/- SEM = 634 /- 175 x 10(3)/mm(2) vessel surface, cf. 329 +/- 69 x 10(3)/mm(2) vessel su rface in untreated rabbits, P = 0.05), with the number of neuroeffector jun ctions remaining the same (124 +/- 14 and 164 +/- 32 x 10(3)/mm(2) vessel s urface) and significantly more non-contacting varicosities (i.e. lying > 10 0 nm from the medial cells) (74 +/- 5% and 25 +/- 7%, respectively; P = 0.0 03). Thus, there was no reduction in the innervation of afferent arterioles in which the smooth muscle cells had changed phenotype in response to enal april treatment as hypothesised. Instead, it would appear that proliferatio n of the innervation had occurred, with the formation of additional varicos ities but these varicosities failed to form neuromuscular junctions. This s tudy has identified a form of neural plasticity in the kidney that has not previously been described. (C) 1999 Elsevier Science B.V. All rights reserv ed.