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Sexual dimorphism in the intrarenal homeostasis of angiotensin (Ang) peptides may influence blood pressure control. Aminopeptidase A (APA) and aminopeptidase N (APN) catalyse the degradation of AngII and AngIII, respectively, but sex differences in their intrarenal expression are equivocal. The aim of this study was to determine if sex differences in renal APA and APN expression contribute to hypertensive kidney injury in mice. Mean arterial pressure (MAP) was measured via radiotelemetry in 5-month-old male and female C57bl/6 mice during baseline and 28-day infusion of vehicle (saline) or AngII (600 ng/kg/min s.c.; n=5-11/group). Glomerular filtration rate (transcutaneous FITC-sinistrin clearance) and protein excretion (24h metabolic cages) were assessed at baseline and end of AngII infusion. Kidneys were fixed for histological assessment of senescence-associated β-galactosidase (a cellular senescence marker), tubulointerstitial fibrosis, tubular dilation and glomerulosclerosis. APA and APN abundance in renal compartments were quantified via immunostaining (glomeruli, cortex, medulla) and Western blotting (cortical homogenates). All histological analyses were performed by a researcher blinded to experimental groups. Baseline MAP and GFR were similar between all groups. Pressor responsiveness to AngII was augmented in males compared to females (27 ± 4 mmHg vs 16 ± 2 mmHg respectively, on day 28; P=0.04). GFR was not affected by AngII infusion in either sex. AngII induced proteinuria (1.5-fold greater than vehicle; P=0.03), glomerular hypertrophy (P This work was funded by an ECR Transition Grant awarded to Dr Walton by the Foundation for High Blood Pressure Research. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Children with solitary functioning kidney (SFK) have an increased risk of hypertension and kidney injury from early in life. Hypertrophy and hyperfiltration are compensatory adaptations in the remaining kidney that may contribute to kidney injury over time. Angiotensin-converting enzyme inhibitors (ACEi) have reno-protective and blood pressure (BP) lowering properties. This study examined if brief ACEi early in life in sheep born with a SFK altered compensatory kidney hypertrophy and prevented elevation in BP and albuminuria. SFK was induced by unilateral nephrectomy in male fetal sheep at 100 days gestation (term=150 days; n=19) or sham surgery performed (n=10). Between 4 to 8 weeks, some SFK lambs received enalapril (n=10; 0.5mg/kg/day, once daily, orally) and others received vehicle (water; n=9). At 2, 6 and 20 months kidney volume was assessed using magnetic resonance imaging. At 8, 14 and 20 months, BP, renal functional reserve and albuminuria were examined. In SFK sheep, kidney volume was lower (~20%) than sham at 2 and 6 months but similar at 20 months. ACEi in SFK sheep reduced kidney volume at 2 months (~13%) but not at 6 or 20 months. SFK sheep had higher BP than sham at all ages and ACEi did not prevent the rise in BP. SFK sheep had higher urinary albumin and reduced RFR at all ages compared with sham. ACEi increased RFR and prevented albuminuria at 8 months in sheep with SFK but not at 14 and 20 months. In conclusion, brief and early ACEi in sheep with SFK did not prevent elevations in BP but delayed the onset of kidney injury in the short-term. This was likely associated with a reduction in the level of kidney hypertrophy early in life. Brief postnatal ACEi may delay loss of renal function in children born with one kidney and warrants further investigation. The Netherlands Organization for Health Research and Development (ZonMW Vidi 016.156.454) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The time course of the renal blood flow and GFR responses to narrowing of the renal artery in conscious dogs is reviewed. The initial response to this threat to renal perfusion is renal vasodilatation, but within minutes a secondary vasoconstriction mediated by angiotensin II begins to develop. Angiotensin II-mediated contraction of mesangial cells is also demonstrable, but this does not apparently reduce the filtration surface area of the glomerular capillaries. The intrarenal effects of angiotensin II restore GFR back to normal within one to two weeks, by which time circulating plasma angiotensin II levels are no longer elevated. In contrast to its effects on GFR, angiotensin II has minimal effects on renal blood flow after stenosis. This may be because, (i) blood flow is mainly determined by the hydraulic resistance of the stenosis; (ii) renal vasoconstriction has relatively little effect on flow due to the particular hemodynamic properties of the stenoses, and (iii) a major site of action of angiotensin II may be within the glomerulus. Thus angiotensin II has a homeostatic role in the maintenance of GFR during renal artery narrowing and one component of this role may involve mesangial contraction.