Appropriate Regulation of Human Renin Gene Expression and Secretion in 45-kb Human Renin Transgenic Mice by Yan Yan, Lufei Hu, Rong Chen, Jean E. Sealey, John H. Laragh, and Daniel F. Catanzaro Hypertension Volume 32(2):205-214 August 1, 1998 Copyright © American Heart Association, Inc. All rights reserved.

A, Human and mouse PRC and ProRC in response to dietary salt: medium, 0.28% NaCl (MED; n=5); high, 8% NaCl (n=5); and low, 0.014% NaCl (n=4). *P<0.0001 and +P<0.005, compared with low salt (Scheffé’s test). A, Human and mouse PRC and ProRC in response to dietary salt: medium, 0.28% NaCl (MED; n=5); high, 8% NaCl (n=5); and low, 0.014% NaCl (n=4). *P<0.0001 and +P<0.005, compared with low salt (Scheffé’s test). B, Effects of captopril on human and mouse PRC and ProRC: control, 0.28% NaCl diet (n=5); captopril, 0.28% NaCl diet plus captopril 0.5 mg/mL in drinking water. *P<0.0001, +P<0.005, †P<0.05, compared with control (Scheffé’s test). Open bars indicate nontransgenic mice; hatched bars, transgenic mice. Yan Yan et al. Hypertension. 1998;32:205-214 Copyright © American Heart Association, Inc. All rights reserved.

RNase protection assay of renal RNA for animals fed salt-modified diets (A) and treated with captopril (B). RNase protection assay of renal RNA for animals fed salt-modified diets (A) and treated with captopril (B). The positions of hREN-, mRen-1C–, and 18S rRNA–specific protection products are indicated. Numbers at the bottom of the figure indicate the amount of human or mouse renin mRNA in each sample (arbitrary unit, normalized by the amount of 18S rRNA). Exposure time was 16 hours. Quantification of renal renin RNA levels in animals fed different salt diets (C) and in captopril-treated mice (D). Data were quantified from RNase protection assays shown in panels A and B after normalization from measurements of samples run in both assays. *P<0.0001 compared with control; †P<0.05 compared with low salt. Open bars indicate nontransgenic; hatched bars, transgenic. Yan Yan et al. Hypertension. 1998;32:205-214 Copyright © American Heart Association, Inc. All rights reserved.

Serial sections of kidneys from a transgenic mouse fed a normal salt diet (control) and a transgenic mouse treated with captopril for 16 days. Serial sections of kidneys from a transgenic mouse fed a normal salt diet (control) and a transgenic mouse treated with captopril for 16 days. Panels A, B, E, and F were from the control mouse; and panels C, D, G, and H were from the captopril-treated mouse. Panels A, C, E, and G stained for both mouse and human renin (BR1-5); and panels B, F, D, and H stained for human renin (R15). Upper panels (A–D) are from lower power magnification (×6), and lower panels (E–H) are central portions of the upper panels at higher magnification (×40). Yan Yan et al. Hypertension. 1998;32:205-214 Copyright © American Heart Association, Inc. All rights reserved.

β-Adrenergic control of human and mouse renin secretion. β-Adrenergic control of human and mouse renin secretion. S indicates saline; P, propranolol; I, isoproterenol; and P+I, propranolol followed by isoproterenol. *P<0.0001 compared with I. Open bars indicate nontransgenic; hatched bars, transgenic. Yan Yan et al. Hypertension. 1998;32:205-214 Copyright © American Heart Association, Inc. All rights reserved.

A, Continuous femoral blood pressure tracing in an anesthetized male mouse. A, Continuous femoral blood pressure tracing in an anesthetized male mouse. NxRP indicates nephrectomized rat plasma. Effect of intravenous infusion of AGT on plasma AGT (AOGN) (B), blood pressure (C), mouse PRC (D), and human PRC (E) in anesthetized male transgenic mice. AGT levels are shown as actual values. For other parameters, measurements taken 15 minutes after the initiation of the saline infusion were used as controls. Subsequent measurements were normalized to control levels and expressed as percentages. Nephrectomized rat plasma or human AGT were added to the infusion between 0 and 30 minutes (indicated by the solid bar). +P<0.001; †P<0.05. Yan Yan et al. Hypertension. 1998;32:205-214 Copyright © American Heart Association, Inc. All rights reserved.

Relationship of human PRC to mouse PRC for all experiments reported in the present study. Yan Yan et al. Hypertension. 1998;32:205-214 Copyright © American Heart Association, Inc. All rights reserved.

Relationship of ProRC, PRC, and TRC to renal renin mRNA levels for the data shown in Figures 1, 2, and 5. Relationship of ProRC, PRC, and TRC to renal renin mRNA levels for the data shown in Figures 1, 2, and 5. Human plasma renin levels are plotted against human renal mRNA, and mouse plasma renin levels are plotted against mouse renal renin mRNA. Yan Yan et al. Hypertension. 1998;32:205-214 Copyright © American Heart Association, Inc. All rights reserved.