Late fetal and newborn granulopoiesis but not active renin is increased by maternal captopril treatment during perinatal kidney development

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Buckley, C and L'Huillier, N and Mullins, L and Semprini, S and Christian, H and Mullins, JJ (2022) Late fetal and newborn granulopoiesis but not active renin is increased by maternal captopril treatment during perinatal kidney development. Preprint / Working Paper. bioRxiv, Long Island, NY. (https://doi.org/10.1101/2022.05.15.491999)

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Abstract

Renin expression follows vascular development through the mouse kidney, regressing to glomerular poles by about P10, where renin is stored in dense core granules in juxtaglomerular cells. Homeostatic challenge to blood pressure causes release of active renin from the granules and recruitment of the renin lineage cells. We investigated the response to homeostatic challenge during late fetal development and following birth in a transgenic line expressing GFP under the renin promotor. Pregnant females were treated with water or captopril (30mg/kg/day), which inhibits angiotensin converting enzyme, from E15.5. We found an increase in renin transcription and expression by P1 following captopril treatment, with granulation increased at the glomerular poles and major arteries from E18.5. At P1, the granules showed a wide variation in electron density. Notably, rough endoplasmic reticulum was expanded in vascular smooth muscle cells (VSMCs) of captopril-treated pups at both time-points suggesting increased transcriptional activity. Paracrystalline material was observed in granules of captopril treated fetuses at E18.5 and in both treated and untreated pups at P1. Renin expression and some granules were confirmed in the kidney VSMCs by immuno-gold staining against GFP at E18.5. Importantly, we found no difference in active renin content between kidneys from treated and untreated pups at either age group. We therefore demonstrate a disconnect between granulation and active renin production in newborns when exposed to homeostatic challenge in utero.

ORCID iDs

Buckley, C ORCID logoORCID: https://orcid.org/0000-0002-7961-4544, L'Huillier, N, Mullins, L, Semprini, S, Christian, H and Mullins, JJ;
CORE (COnnecting REpositories)