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Fig 1.

Study timeline of the 5/6 nephrectomy animal model of chronic kidney disease.

Treatment (Rx): ACEI (Enalapril 10mg/kg) or CCB (Diltiazem 30mg/kg) started at 10 weeks post-surgery and all parameters assessed at 18–20 weeks post-surgery. SBP: systolic blood pressure; RBF: renal blood flow; MBF: myocardial blood flow; RIA: radioimmunoassay.

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Fig 1 Expand

Fig 2.

Body weight data obtained weekly over 10 weeks (A), terminal left kidney weight for sham (N = 8), Nx (N = 8), NxE (N = 6) and NxD (N = 8) (B) and heart weight for sham (N = 8), Nx (N = 9), NxE (N = 9) and NxD (N = 8) (C) normalized to body weight at 18–20 weeks post-surgery. Data are presented as mean±SD. * p<0.05 vs sham, $ p<0.05 vs Nx, # p<0.05 vs NxE (p<0.05).

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Fig 2 Expand

Table 1.

SBP, plasma creatinine (Cr) and urinary albumin:Cr in sham, untreated Nx, NxE and NxD (at 18–20 weeks post-surgery).

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Table 1 Expand

Fig 3.

Ang II levels in plasma samples of sham (N = 4), Nx (N = 5), NxE (N = 5) and NxD (N = 6) (A), left kidney samples of sham (N = 5), Nx (N = 6), NxE (N = 5) and NxD (N = 5) (B) and left ventricle samples of sham (N = 6), Nx (N = 7), NxE (N = 5) and NxD (N = 6) (C) samples of Sham, Nx, NxE and NxD groups at 18–20 weeks post-surgery. In boxplots, horizontal lines represent median and whiskers represent minimum and maximum values. Data are presented as mean±SD. * p<0.05 vs sham, $ p<0.05 vs Nx, # p<0.05 vs NxE (p<0.05).

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Fig 3 Expand

Fig 4.

Representative coronal view microPET scans showing liver and kidney uptake obtained at 5–10 min post-injection of [18F]FPyr-losartan in all groups at 18–20 weeks post-surgery; Sham (A), Nx (B), NxE (C) and NxD (D). Images are displayed using same SUV scale. Kidney distribution volume (DV, ml/cm3) of [18F]FPyr-losartan obtained with PET in vivo in sham (N = 6), Nx (N = 7), NxE (N = 7) and NxD (N = 6) (E); and 125I-[Sar1, Ile8]Ang II binding density (counts/mm2) obtained with in vitro autoradiography in sham (N = 4), Nx (N = 4), NxE (N = 6) and NxD (N = 4) (F) at 18–20 weeks post-surgery. In boxplots, horizontal lines represent median and whiskers represent minimum and maximum values. Data are presented as mean±SD. * p<0.05 vs sham, $ p<0.05 vs Nx, # p<0.05 vs NxE (p<0.05).

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Fig 4 Expand

Fig 5.

Renal blood flow in sham (N = 7), Nx (N = 7), NxE (N = 5) and NxD (N = 7) groups (A); and myocardial blood flow values in sham (N = 6), Nx (N = 5), NxE (N = 6) and NxD (N = 5) (B) at 18–20 weeks post-surgery. Blood flow was assessed by [13N]ammonia PET imaging. In boxplots, horizontal lines represent median and whiskers represent minimum and maximum values. Data are presented as mean±SD. * p<0.05 vs sham, $ p<0.05 vs Nx, # p<0.05 vs NxE (p<0.05).

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Fig 5 Expand

Table 2.

Echocardiographic parameters in sham, untreated Nx, NxE and NxD groups at 18–20 weeks post-surgery.

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Table 2 Expand