Journal: American journal of physiology. Renal physiology

Article Title: A Key Role of AT 1a Receptors and Na + /H + Exchanger 3 in The Proximal Tubules in Angiotensin II-induced and Two-Kidney, One-Clip Goldblatt Hypertension

doi: 10.1152/ajprenal.00122.2025

Figure Lengend Snippet: Baseline general physiological phenotypes of mutant mice with double deletion of the AT 1a receptor and Na + /H + exchanger 3 (NHE3) selectively in the proximal tubules of the kidney in adult male PT- Agtr1a −/− /PT- Nhe3 −/− mice. A: Body wt.; B: Heart wt./body wt. ratio; C: Kidney wt./body wt. ratio; and D: Hematocrit. No significant differences were found between age- and body wt.-matched adult male WT and PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice.

Article Snippet: We originally obtained the iL1- Sglt2-Cre mice from Rubera et al. ( 36 ), Nhe3 fl/fl mice from Li et al. ( 37 ), and Agtr1a -floxed mice, C57BL/6N- Agtr1a tm1Uky/J (Stock No: 016211), from Jackson laboratories, respectively ( 38 ).

Techniques: Mutagenesis, Double Knockout

Journal: American journal of physiology. Renal physiology

Article Title: A Key Role of AT 1a Receptors and Na + /H + Exchanger 3 in The Proximal Tubules in Angiotensin II-induced and Two-Kidney, One-Clip Goldblatt Hypertension

doi: 10.1152/ajprenal.00122.2025

Figure Lengend Snippet: Baseline kidney physiological phenotypes of mutant mice with double deletion of the AT 1a receptor and Na + /H + exchanger 3 (NHE3) selectively in the proximal tubules of the kidney in adult male PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice. Basal whole-kidney glomerular filtration rate (Panel A: GFR), 24 h urine excretion (Panel B), urinary sodium (Panel C) and potassium excretion (Panel D) were significantly higher in age- and body wt.-matched adult male PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice than WT mice. * P <0.05 or ** P <0.01 vs. WT.

Article Snippet: We originally obtained the iL1- Sglt2-Cre mice from Rubera et al. ( 36 ), Nhe3 fl/fl mice from Li et al. ( 37 ), and Agtr1a -floxed mice, C57BL/6N- Agtr1a tm1Uky/J (Stock No: 016211), from Jackson laboratories, respectively ( 38 ).

Techniques: Mutagenesis, Double Knockout, Filtration

Journal: American journal of physiology. Renal physiology

Article Title: A Key Role of AT 1a Receptors and Na + /H + Exchanger 3 in The Proximal Tubules in Angiotensin II-induced and Two-Kidney, One-Clip Goldblatt Hypertension

doi: 10.1152/ajprenal.00122.2025

Figure Lengend Snippet: Glomerular and proximal tubular ultracellular structures in adult male WT, single gene PT- Agtr1a −/− , PT- Nhe3 −/− , or PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice. Panels A to H represent high-resolution electron microscopic (EM) micrographs showing the ultracellular structures of representative glomeruli (Direct Mag: 1,000X) and proximal tubules (Direct Mag: 2,500X) in adult male WT (A, E), PT- Agtr1a −/− (B, F), and PT- Nhe3 −/− (C, G) and PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice (D, H). No marked differences were observed in glomerular endothelial, epithelial, mesangial, and podocyte cells, and proximal tubular ultracellular structures between WT, single gene PT- Agtr1a −/− , PT- Nhe3 −/− , and PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice. Abbreviations: AP, apical membrane; BM, basement membrane; E, fenestrated endothelial cell; GBM, glomerular basement membrane; M, mesangial cell; Mito, mitochondrion; MV, microvillar; N, nucleus; PE, parietal epithelial cell; PO, podocyte.

Article Snippet: We originally obtained the iL1- Sglt2-Cre mice from Rubera et al. ( 36 ), Nhe3 fl/fl mice from Li et al. ( 37 ), and Agtr1a -floxed mice, C57BL/6N- Agtr1a tm1Uky/J (Stock No: 016211), from Jackson laboratories, respectively ( 38 ).

Techniques: Double Knockout, Membrane

Journal: American journal of physiology. Renal physiology

Article Title: A Key Role of AT 1a Receptors and Na + /H + Exchanger 3 in The Proximal Tubules in Angiotensin II-induced and Two-Kidney, One-Clip Goldblatt Hypertension

doi: 10.1152/ajprenal.00122.2025

Figure Lengend Snippet: The development of Ang II-induced or two-kidney, one-clip (2K1C) Goldblatt hypertension in adult male and female WT and PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice. Panels A, B, E & F compare Ang II-induced hypertensive responses between male and female WT and PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice, whereas Panels C, D, G & H compare 2K1C-induced hypertensive responses between male and female WT and PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice. ** P <0.01 vs. control of the respective WT and PT- Agtr1a −/− /PT- Nhe3 −/− mice. Note that baseline systolic blood pressure was significantly lower, and the blood pressure response to Ang II infusion was attenuated by about 50% in both male and female PT- Agtr1a −/− /PT- Nhe3 −/− mice than WT mice. By contrast, the development of 2K1C Goldblatt hypertension was blocked in both male and female PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice. ++ P <0.01 vs. Control WT.

Article Snippet: We originally obtained the iL1- Sglt2-Cre mice from Rubera et al. ( 36 ), Nhe3 fl/fl mice from Li et al. ( 37 ), and Agtr1a -floxed mice, C57BL/6N- Agtr1a tm1Uky/J (Stock No: 016211), from Jackson laboratories, respectively ( 38 ).

Techniques: Double Knockout, Control

Journal: American journal of physiology. Renal physiology

Article Title: A Key Role of AT 1a Receptors and Na + /H + Exchanger 3 in The Proximal Tubules in Angiotensin II-induced and Two-Kidney, One-Clip Goldblatt Hypertension

doi: 10.1152/ajprenal.00122.2025

Figure Lengend Snippet: The effects of the induction of 2K1C Goldblatt hypertension on glomerular filtration rate (GFR) in adult male and female WT, single gene PT- Agtr1a −/− or PT- Nhe3 −/− knockout and PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice. Panels A to D show the GFR responses in adult male WT, single gene PT- Agtr1a −/− or PT- Nhe3 −/− knockout, and PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice, whereas Panels E-H show the GFR responses in adult female WT, single gene PT- Agtr1a −/− or PT- Nhe3 −/− knockout, and PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice, respectively. * P <0.05 or ** P <0.01 vs. control. + P <0.05 or ++ P <0.01 vs. Control WT.

Article Snippet: We originally obtained the iL1- Sglt2-Cre mice from Rubera et al. ( 36 ), Nhe3 fl/fl mice from Li et al. ( 37 ), and Agtr1a -floxed mice, C57BL/6N- Agtr1a tm1Uky/J (Stock No: 016211), from Jackson laboratories, respectively ( 38 ).

Techniques: Filtration, Knock-Out, Double Knockout, Control

Journal: American journal of physiology. Renal physiology

Article Title: A Key Role of AT 1a Receptors and Na + /H + Exchanger 3 in The Proximal Tubules in Angiotensin II-induced and Two-Kidney, One-Clip Goldblatt Hypertension

doi: 10.1152/ajprenal.00122.2025

Figure Lengend Snippet: Comparisons of systolic blood pressure responses to systemic ACE inhibition or AT 1 receptor blockade in adult male and female WT and PT- Agtr1a −/− /PT- Nhe3 −/− mice. Panels A, B & E show systolic blood pressure responses to systemic ACE inhibition with captopril (25 mg/kg/day, p.o., 2 weeks) in male and female WT and PT- Agtr1a −/− /PT- Nhe3 −/− mice, whereas Panels C, D & F show systolic blood pressure responses to systemic AT 1 receptor blockade with losartan (20 mg/kg/day, p.o., 2 weeks) in male and female WT and PT- Agtr1a −/− /PT- Nhe3 −/− mice. Both captopril and losartan significantly decreased systolic blood pressure in adult male and female WT and PT- Agtr1a −/− /PT- Nhe3 −/− mice (** P <0.01 vs. Control), but the responses were attenuated in PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice ( P <0.05). ++ P <0.01 vs. Control WT.

Article Snippet: We originally obtained the iL1- Sglt2-Cre mice from Rubera et al. ( 36 ), Nhe3 fl/fl mice from Li et al. ( 37 ), and Agtr1a -floxed mice, C57BL/6N- Agtr1a tm1Uky/J (Stock No: 016211), from Jackson laboratories, respectively ( 38 ).

Techniques: Inhibition, Control, Double Knockout

Journal: American journal of physiology. Renal physiology

Article Title: A Key Role of AT 1a Receptors and Na + /H + Exchanger 3 in The Proximal Tubules in Angiotensin II-induced and Two-Kidney, One-Clip Goldblatt Hypertension

doi: 10.1152/ajprenal.00122.2025

Figure Lengend Snippet: The effect of treatment with high salt diet for 4 weeks on systolic blood pressure and 24-h urinary sodium excretion in adult male WT, PT- Agtr1a −/− , PT- Nhe3 −/− , and PT- Agtr1a −/− /PT- Nhe3 −/− mice. High salt treatment for 2 weeks significantly increased the natriuretic response, but had no significant effects on systolic blood pressure in adult male WT (A), PT- Agtr1a −/− (B), PT- Nhe3 −/− (C), and PT- Agtr1a −/− /PT- Nhe3 −/− mice (D), suggesting that the proximal tubule AT 1a /NHE3 signal pathway unlikely plays an important role in the development of high salt-induced hypertension. *** P <0.001 or **** P <0.0001 vs. Control.

Article Snippet: We originally obtained the iL1- Sglt2-Cre mice from Rubera et al. ( 36 ), Nhe3 fl/fl mice from Li et al. ( 37 ), and Agtr1a -floxed mice, C57BL/6N- Agtr1a tm1Uky/J (Stock No: 016211), from Jackson laboratories, respectively ( 38 ).

Techniques: Control

Journal: American journal of physiology. Renal physiology

Article Title: A Key Role of AT 1a Receptors and Na + /H + Exchanger 3 in The Proximal Tubules in Angiotensin II-induced and Two-Kidney, One-Clip Goldblatt Hypertension

doi: 10.1152/ajprenal.00122.2025

Figure Lengend Snippet: Schematic illustration showing double deletion of AT 1a receptors and NHE3 selectively in the proximal tubules of the kidney markedly attenuates the development of Ang II-induced and 2K1C Goldblatt hypertension in PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice. The data of the present study provides strong evidence for a key role of the Ang II/AT 1a /NHE3 signaling pathways in the proximal tubules in maintaining physiological blood pressure homeostasis and the development of Ang II-induced and 2K1C Goldblatt hypertension. +, iL1- Sglt2-Cre/Agtr1a flox/flox mice cross bred with iL1- Sglt2-Cre/Nhe3 flox/flox mice to generate PT- Agtr1a −/− /PT- Nhe3 −/− double gene knockout mice.

Article Snippet: We originally obtained the iL1- Sglt2-Cre mice from Rubera et al. ( 36 ), Nhe3 fl/fl mice from Li et al. ( 37 ), and Agtr1a -floxed mice, C57BL/6N- Agtr1a tm1Uky/J (Stock No: 016211), from Jackson laboratories, respectively ( 38 ).

Techniques: Double Knockout, Protein-Protein interactions