Granular juxtaglomerular cells and prorenin synthesis in mice treated with enalapril.
The short-term and long-term effects (for up to 98 days) of the angiotensin converting enzyme inhibitor enalapril were investigated in male and female BALB/c mice. In control animals, separate antisera to renin and its prosequence produced an identical pattern of staining in granular cells of the juxtaglomerular apparatus (JGA) a short distance from the glomerulus. After 1 day of the enalapril treatment there was a decrease in the number of JGA granular cells immunostained with antisera to both renin and its prosequence. Electron microscopy revealed degranulation of mature granules from JGA granular cells. Fusion of granules with the cell membrane was not observed, but numerous membrane-like structures (myelin figures) were identified in the cytoplasm and extracellular space, indicating possible secretion. In addition, the volume proportion of granulated cells in relation to the glomerular volume was decreased, as was renal renin content. With continuing enalapril treatment, separate antisera to renin and its prosequence stained the same granulated JGA cells with equal intensity. The cells so stained increased in number, extending down the wall of the afferent arteriole to cortical radial arteries (interlobular arteries) upstream from the glomerulus. Ultrastructural studies revealed a progressive development of cytoplasmic granulation in JGA granular cells and in smooth muscle cells extending into cortical radial arteries. Furthermore, the volume proportion of granulated cells in relation to the glomerular volume was significantly increased, as was renal renin content. Thus, short-term enalapril treatment in mice provoked rapid secretion of renin via degranulation of mature granules from JGA granular cells. In contrast, long-term enalapril treatment produced a continuing stimulus for renin synthesis, secretion and storage, resulting in an increased thickness of the afferent arteriolar wall. The mechanism for this change appears to be hypertrophy and hypergranulation of granular JGA cells and neogranulation of smooth muscle cells upstream from the glomerulus. Identification of the intrarenal mediators that induce these phenotypic changes presents an interesting challenge.
Berka
J L
JL
Department of Anatomy, University of Melbourne, Parkville, Victoria, Australia.
Alcorn
D
D
Coghlan
J P
JP
Fernley
R T
RT
Morgan
T O
TO
Ryan
G B
GB
Skinner
S L
SL
Weaver
D A
DA
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology*; D004792:Enzyme Precursors / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D012077:Renal Artery; D012083:Renin / Q000096:biosynthesis* / Q000378:metabolism; D013997:Time Factors
D004792:Enzyme Precursors; D004656:Enalapril; D012083:Renin