ACE inhibition attenuates, whereas high-salt intake does not aggravate endothelial damage in mice with renin cell-specific Gsα knockout

Transgenic mice with inducible Gsα knockout in renin-producing cells (RPC-GsKO) develop a complex adverse renal phenotype. We hypothesized that modulation of renin production would also modulate the endothelial damage in this model. RPC-GsKO mice and inbred wild type littermates (WT) were used. Three months after knockout induction (baseline), uninephrectomy was performed to aggravate the renal phenotype. Afterwards, mice remained untreated (controls) or were treated for three months with either the angiotensin-converting-enzyme inhibitor (ACEi) enalapril or high-salt diet to stimulate or inhibit renin production, respectively. Kidney function was assessed. At the end of the experiments renal injury was evaluated by immune cell infiltration and immunofluorescent staining for the endothelial marker endomucin. At baseline, RPC-GsKO mice displayed increased renal vascular resistance. Uninephrectomy lead to a transient decrease in the renal vascular resistance in untreated and high-salt treated RPC-GsKO animals. Glomerular filtration rate (GFR) was lower in RPC-GsKO mice at baseline. In the high-salt RPC-GsKO group, GFR decreased only insignificantly after uninephrectomy. Renal immune cell infiltration in the high-salt diet groups featured a higher number of CD8+ cells in RPC-GsKO mice. Finally, renal endothelial injury in RPC-GsKO mice was abolished by ACEi and not potentiated by high-salt diet as estimated by endomucin staining.