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Ultrastructural Juxtaglomerular Cell Changes in Normotensive Rats Treated with Quinapril, an Inhibitor of Angiotensin-Converting Enzyme

Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co., Ann Arbor, Michigan 48105

Walter F. Bobrowski

Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co., Ann Arbor, Michigan 48105

Alan L. Mvetz

Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co., Ann Arbor, Michigan 48105

Alec W. Gough

Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co., Ann Arbor, Michigan 48105

John R. MacDonald

Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co., Ann Arbor, Michigan 48105

Sequential histologic and ultrastructural changes in juxtaglomerular apparatus (JGA) were defined in male rats treated with quinapril, an inhibitor of angiotensin-converting enzyme (ACE). Doses of 0, 10, 100, and 400 mg/kg were administered daily by gavage for up to 4 weeks. Granular juxtaglomerular (JG) cells were normal or hypogranular on Day 1 at all doses and were hypergranular by Day 7 in rats given 100 and 400 mg/kg relative to age-matched controls. Histologically, JGA hypertrophy was apparent by Day 7 at all doses and was most pronounced by Day 14 in intermediate and deep cortical zones of rats given 100 and 400 mg/kg. Ultrastructurally, hypertrophic JG cells had abundant rough endoplasmic reticulum and free ribosomes, and prominent Golgi complexes associated with numerous cytoplasmic coated vesicles. Dose-dependent increases in numbers of protogranules, altered granules, and cytoplasmic vacuoles occurred in association with decreased size and increased pleomorphism of mature secretory granules. Granule alterations included vesicular to lamellar membranous matrical inclusions, irregular patterns of osmiophilia, matrical vacuolation, and flocculent to coarsely granular matrix of greater density than mature granules. We concluded that JG cell hypertrophy and hyperplasia occurred rapidly in response to subchronic ACE inhibition. Further, ultra-structural changes in JG cells were indicative of stimulated renin synthesis by a regulated pathway, renin secretion by exocytosis and cytoplasmic solubilization of granules, and autophagy of granules as a mechanism whereby JG cells regulate levels of stored renin under conditions of excessive stimulation.

Key Words: Quinapril • ACE inhibition • Wistar rat • juxtaglomerular apparatus • afferent arteriole • JG cell hypertrophy • JG cell hyperplasia

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Toxicologic Pathology, Vol. 18, No. 3, 396-406 (1990)
DOI: 10.1177/019262339001800306


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Dominick, M. A. Articles by MacDonald, J. R. Search for Related Content PubMed PubMed Citation Articles by Dominick, M. A. Articles by MacDonald, J. R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB QUINAPRIL HYDROCHLORIDE Social Bookmarking                         What's this?