Adenovirus-mediated kallikrein gene delivery reverses salt-induced renal injury in Dahl salt-sensitive rats Julie Chao, Jenny J. Zhang, Kuei-Fu Lin, Lee Chao Kidney International Volume 54, Issue 4, Pages 1250-1260 (October 1998) DOI: 10.1046/j.1523-1755.1998.00104.x Copyright © 1998 International Society of Nephrology Terms and Conditions
Figure 1 Systolic blood pressure of Dahl-SS rats after i.v. injection of Ad.CMV-cHK and Ad.CMV-LacZ. Control, Dahl-SS rats (□) were fed a normal salt diet (0.4% NaCl); Dahl-SS rats were fed a high salt diet (4% NaCl), receiving control adenovirus, Ad.CMV-LacZ or adenovirus carrying the human kallikrein gene, Ad.CMV-cHK (▪). Blood pressure values are expressed as mean ± sem (N = 6). Standard errors are shown by bars. Kidney International 1998 54, 1250-1260DOI: (10.1046/j.1523-1755.1998.00104.x) Copyright © 1998 International Society of Nephrology Terms and Conditions
Figure 2 Expression of human kallikrein mRNA in Dahl-SS rats after human kallikrein gene delivery. The rats were sacrificed at 12days post injection and one μg of RNA was used for RT-PCR. Human kallikrein mRNA in rat tissues was amplified by a set of specific oligonucleotides for human tissue kallikrein which yielded a partial cDNA (503bp) product as shown in the upper panel. Rat β-actin mRNA in rat tissues was amplified by a set of specific oligonucleotides which yielded a 500bp product as shown in the lower panel. RNAs from heart, kidney, aorta and liver of rats receiving Ad.CMV-cHK of Ad.CMV-LacZ are indicated in the Figure. Kidney International 1998 54, 1250-1260DOI: (10.1046/j.1523-1755.1998.00104.x) Copyright © 1998 International Society of Nephrology Terms and Conditions
Figure 3 Left ventricular weight (A) and cardiomyocyte diameter (B) of Dahl-SS rats after adenovirus-mediated kallikrein gene delivery. Control, on a normal salt diet (0.4% NaCl); Ad.CMV-LacZ, (4% NaCl) receiving control adenovirus carrying the LacZ gene; Ad.CMV-cHK, (4% NaCl) receiving adenovirus carrying the human kallikrein gene. Kidney International 1998 54, 1250-1260DOI: (10.1046/j.1523-1755.1998.00104.x) Copyright © 1998 International Society of Nephrology Terms and Conditions
Figure 4 Histological sections of heart stained with hematoxylin and eosin. (A) Control, Dahl-SS rat fed a normal salt diet (0.4% NaCl). (B) Dahl-SS rat fed a high salt diet (4% NaCl) for four weeks. (C) Dahl-SS rat fed a high salt diet (4% NaCl) for four weeks, then given control adenovirus, Ad.CMV-LacZ, two weeks prior to sacrifice. (D) Dahl-SS rat fed a high salt diet (4% NaCl) for four weeks, then given adenovirus, Ad.CMV-cHK carrying the human tissue kallikrein gene, two weeks prior to sacrifice. Interstitial proliferation among enlarged cardiomyocytes is indicated by an arrow (magnification ×125). Kidney International 1998 54, 1250-1260DOI: (10.1046/j.1523-1755.1998.00104.x) Copyright © 1998 International Society of Nephrology Terms and Conditions
Figure 5 Glomerular filtration rate (A) and renal blood flow (B) of Dahl-SS rats after adenovirus-mediated kallikrein gene delivery. Control, on a normal salt diet (0.4% NaCl); Ad.CMV-LacZ, (4% NaCl) receiving control adenovirus carrying the LacZ gene; Ad.CMV-cHK, (4% NaCl) receiving adenovirus carrying the human kallikrein gene. The renal functional study was performed at two weeks after gene delivery. Kidney International 1998 54, 1250-1260DOI: (10.1046/j.1523-1755.1998.00104.x) Copyright © 1998 International Society of Nephrology Terms and Conditions
Figure 6 Photomicrographs of representative hematoxylin and eosin-stained renal cortex sections. (A) Control, Dahl-SS rat, fed on a normal salt diet (0.4% NaCl). (B) Dahl-SS rat, fed a high salt diet (4% NaCl) for four weeks. (C) Dahl-SS rat fed a high salt diet (4% NaCl) for four weeks, then given control adenovirus, Ad.CMV-LacZ two weeks prior to sacrifice. (D) Dahl-SS rat fed a high salt diet (4% NaCl) for four weeks, then given adenovirus, Ad.CMV-cHK carrying the human tissue kallikrein gene two weeks prior to sacrifice. Note dilated proximal tubules in B and C and glomerular sclerosis in C (magnification ×100). Kidney International 1998 54, 1250-1260DOI: (10.1046/j.1523-1755.1998.00104.x) Copyright © 1998 International Society of Nephrology Terms and Conditions
Figure 7 Photomicrographs of representative hematoxylin and eosin-stained renal medulla sections. (A) Control, Dahl-SS rat fed a normal salt diet (0.4% NaCl). (B) Dahl-SS rat, fed on a high salt diet (4% NaCl) for four weeks. (C) Dahl-SS rat fed a high salt diet (4% NaCl) for four weeks, then given control adenovirus, Ad.CMV-LacZ, two weeks prior to sacrifice. (D) Dahl-SS rat fed a high salt diet (4% NaCl) for four weeks, then given adenovirus, Ad.CMV-cHK carrying the human tissue kallikrein gene, two weeks prior to sacrifice. Note the large colloidal casts in medullary tubules of animals given high salt Figure 7b and high salt plus the Lac Z gene Fig. 7c (Magnification ×50). Kidney International 1998 54, 1250-1260DOI: (10.1046/j.1523-1755.1998.00104.x) Copyright © 1998 International Society of Nephrology Terms and Conditions
Figure 8 Protective effect against salt-induced glomerular sclerosis in Dahl-SS rats after kallikrein gene delivery. Control, on a normal salt diet (0.4% NaCl); Ad.CMV-LacZ, (4% NaCl) receiving control adenovirus carrying the LacZ gene; Ad.CMV-cHK, (4% NaCl) receiving adenovirus carrying the human kallikrein gene. Kidney International 1998 54, 1250-1260DOI: (10.1046/j.1523-1755.1998.00104.x) Copyright © 1998 International Society of Nephrology Terms and Conditions
Kidney International 1998 54, 1250-1260DOI: (10. 1046/j. 1523-1755 Kidney International 1998 54, 1250-1260DOI: (10.1046/j.1523-1755.1998.00104.x) Copyright © 1998 International Society of Nephrology Terms and Conditions