Angiotensin II receptor blocker pretreatment of rats undergoing sudden renal ablation

Hye Won Park, Youngki Kim, Kee Hyuck Kim, Silvia Rozen, Behzad Najafian, Michael Mauer

Research output: Contribution to journalArticle

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Abstract

Background.Subtotal nephrectomy (N) in rats results in progressive hypertension, proteinuria and renal lesions. Renin-angiotensin system blockade initiated at N prevents these changes; treatments failing to reduce hypertension and proteinuria do not. Methods.Ten Munich-Wistar rats underwent 1 surgical N; eight littermates were pretreated with losartan (L) only for 6 weeks prior to 1 N (N + L). Pretreated (n = 8; C + L) and untreated controls (C; n = 8) had sham operations. Results.Over 6 months, N and N + L rats developed ∼80% increase in glomerular filtration rate per nephron over C and C + L, P < 0.001). Hypertension (intra-arterial mean blood pressure 116 ± 6.8 mmHg in N rats versus 102 ± 3.2 in C, 104 ± 8.4 in C + L, and 104 ± 8.4 in N + L rats, P < 0.001 for all) and proteinuria (120 ± 20 mg/day in N versus 39 ± 10 in C, 34 ± 8 in C + L and 35 ± 8 in N + L, P < 0.001 for all) developed only in N. Focal segmental glomerulosclerosis (FSGS) (%) at 6 months was 20 ± 8 in N and 17.5 ± 8 in N + L (ns) and <1 in C and C + L (P < 0.001 versus N and N + L). Interstitial fractional volume (Vv), 4.0 ± 1.7% in C and 4.4 ± 1.6% in C + L (ns), was similarly increased to 7.5 ± 2.5% in N and 9.0 ± 3.9% in N+L (P < 0.04 versus C and C + L). Atrophic tubule Vv was increased by >300% in N and N + L over C and C + L (P < 0.02 for all). Glomerular volume doubled in N and N + L (P < 0.001). Podocyte foot process effacement was greater in N and NL than in C or C + L (P ≤ 0.02 for all). Thus, L given for 6 weeks prior to 1 N prevented hypertension and proteinuria over the subsequent 6 months without reducing glomerular hypertrophy, hyperfiltration or interstitial, tubular or FSGS lesions or foot process effacement. Conclusions.These studies dissociated systemic hypertension and proteinuria from the renal lesions in this model. Durable effects of losartan on blood pressure and proteinuria likely represent epigenetic processes.

Original languageEnglish (US)
Pages (from-to)107-114
Number of pages8
JournalNephrology Dialysis Transplantation
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Angiotensin Receptor Antagonists
Proteinuria
Kidney
Renal Hypertension
Losartan
Genetic Epigenesis
Hypertension
Podocytes
Nephrons
Renin-Angiotensin System
Nephrectomy
Glomerular Filtration Rate
Hypertrophy
Wistar Rats
Foot
Blood Pressure

Keywords

  • angiotensin receptor blockade
  • focal segmental glomerulosclerosis
  • hypertension
  • interstitial fibrosis
  • proteinuria
  • renal ablation

Cite this

Angiotensin II receptor blocker pretreatment of rats undergoing sudden renal ablation. / Park, Hye Won; Kim, Youngki; Kim, Kee Hyuck; Rozen, Silvia; Najafian, Behzad; Mauer, Michael.

In: Nephrology Dialysis Transplantation, Vol. 27, No. 1, 01.01.2012, p. 107-114.

Research output: Contribution to journalArticle

Park, Hye Won ; Kim, Youngki ; Kim, Kee Hyuck ; Rozen, Silvia ; Najafian, Behzad ; Mauer, Michael. / Angiotensin II receptor blocker pretreatment of rats undergoing sudden renal ablation. In: Nephrology Dialysis Transplantation. 2012 ; Vol. 27, No. 1. pp. 107-114.
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abstract = "Background.Subtotal nephrectomy (N) in rats results in progressive hypertension, proteinuria and renal lesions. Renin-angiotensin system blockade initiated at N prevents these changes; treatments failing to reduce hypertension and proteinuria do not. Methods.Ten Munich-Wistar rats underwent 1 surgical N; eight littermates were pretreated with losartan (L) only for 6 weeks prior to 1 N (N + L). Pretreated (n = 8; C + L) and untreated controls (C; n = 8) had sham operations. Results.Over 6 months, N and N + L rats developed ∼80{\%} increase in glomerular filtration rate per nephron over C and C + L, P < 0.001). Hypertension (intra-arterial mean blood pressure 116 ± 6.8 mmHg in N rats versus 102 ± 3.2 in C, 104 ± 8.4 in C + L, and 104 ± 8.4 in N + L rats, P < 0.001 for all) and proteinuria (120 ± 20 mg/day in N versus 39 ± 10 in C, 34 ± 8 in C + L and 35 ± 8 in N + L, P < 0.001 for all) developed only in N. Focal segmental glomerulosclerosis (FSGS) ({\%}) at 6 months was 20 ± 8 in N and 17.5 ± 8 in N + L (ns) and <1 in C and C + L (P < 0.001 versus N and N + L). Interstitial fractional volume (Vv), 4.0 ± 1.7{\%} in C and 4.4 ± 1.6{\%} in C + L (ns), was similarly increased to 7.5 ± 2.5{\%} in N and 9.0 ± 3.9{\%} in N+L (P < 0.04 versus C and C + L). Atrophic tubule Vv was increased by >300{\%} in N and N + L over C and C + L (P < 0.02 for all). Glomerular volume doubled in N and N + L (P < 0.001). Podocyte foot process effacement was greater in N and NL than in C or C + L (P ≤ 0.02 for all). Thus, L given for 6 weeks prior to 1 N prevented hypertension and proteinuria over the subsequent 6 months without reducing glomerular hypertrophy, hyperfiltration or interstitial, tubular or FSGS lesions or foot process effacement. Conclusions.These studies dissociated systemic hypertension and proteinuria from the renal lesions in this model. Durable effects of losartan on blood pressure and proteinuria likely represent epigenetic processes.",
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AU - Kim, Youngki

AU - Kim, Kee Hyuck

AU - Rozen, Silvia

AU - Najafian, Behzad

AU - Mauer, Michael

PY - 2012/1/1

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N2 - Background.Subtotal nephrectomy (N) in rats results in progressive hypertension, proteinuria and renal lesions. Renin-angiotensin system blockade initiated at N prevents these changes; treatments failing to reduce hypertension and proteinuria do not. Methods.Ten Munich-Wistar rats underwent 1 surgical N; eight littermates were pretreated with losartan (L) only for 6 weeks prior to 1 N (N + L). Pretreated (n = 8; C + L) and untreated controls (C; n = 8) had sham operations. Results.Over 6 months, N and N + L rats developed ∼80% increase in glomerular filtration rate per nephron over C and C + L, P < 0.001). Hypertension (intra-arterial mean blood pressure 116 ± 6.8 mmHg in N rats versus 102 ± 3.2 in C, 104 ± 8.4 in C + L, and 104 ± 8.4 in N + L rats, P < 0.001 for all) and proteinuria (120 ± 20 mg/day in N versus 39 ± 10 in C, 34 ± 8 in C + L and 35 ± 8 in N + L, P < 0.001 for all) developed only in N. Focal segmental glomerulosclerosis (FSGS) (%) at 6 months was 20 ± 8 in N and 17.5 ± 8 in N + L (ns) and <1 in C and C + L (P < 0.001 versus N and N + L). Interstitial fractional volume (Vv), 4.0 ± 1.7% in C and 4.4 ± 1.6% in C + L (ns), was similarly increased to 7.5 ± 2.5% in N and 9.0 ± 3.9% in N+L (P < 0.04 versus C and C + L). Atrophic tubule Vv was increased by >300% in N and N + L over C and C + L (P < 0.02 for all). Glomerular volume doubled in N and N + L (P < 0.001). Podocyte foot process effacement was greater in N and NL than in C or C + L (P ≤ 0.02 for all). Thus, L given for 6 weeks prior to 1 N prevented hypertension and proteinuria over the subsequent 6 months without reducing glomerular hypertrophy, hyperfiltration or interstitial, tubular or FSGS lesions or foot process effacement. Conclusions.These studies dissociated systemic hypertension and proteinuria from the renal lesions in this model. Durable effects of losartan on blood pressure and proteinuria likely represent epigenetic processes.

AB - Background.Subtotal nephrectomy (N) in rats results in progressive hypertension, proteinuria and renal lesions. Renin-angiotensin system blockade initiated at N prevents these changes; treatments failing to reduce hypertension and proteinuria do not. Methods.Ten Munich-Wistar rats underwent 1 surgical N; eight littermates were pretreated with losartan (L) only for 6 weeks prior to 1 N (N + L). Pretreated (n = 8; C + L) and untreated controls (C; n = 8) had sham operations. Results.Over 6 months, N and N + L rats developed ∼80% increase in glomerular filtration rate per nephron over C and C + L, P < 0.001). Hypertension (intra-arterial mean blood pressure 116 ± 6.8 mmHg in N rats versus 102 ± 3.2 in C, 104 ± 8.4 in C + L, and 104 ± 8.4 in N + L rats, P < 0.001 for all) and proteinuria (120 ± 20 mg/day in N versus 39 ± 10 in C, 34 ± 8 in C + L and 35 ± 8 in N + L, P < 0.001 for all) developed only in N. Focal segmental glomerulosclerosis (FSGS) (%) at 6 months was 20 ± 8 in N and 17.5 ± 8 in N + L (ns) and <1 in C and C + L (P < 0.001 versus N and N + L). Interstitial fractional volume (Vv), 4.0 ± 1.7% in C and 4.4 ± 1.6% in C + L (ns), was similarly increased to 7.5 ± 2.5% in N and 9.0 ± 3.9% in N+L (P < 0.04 versus C and C + L). Atrophic tubule Vv was increased by >300% in N and N + L over C and C + L (P < 0.02 for all). Glomerular volume doubled in N and N + L (P < 0.001). Podocyte foot process effacement was greater in N and NL than in C or C + L (P ≤ 0.02 for all). Thus, L given for 6 weeks prior to 1 N prevented hypertension and proteinuria over the subsequent 6 months without reducing glomerular hypertrophy, hyperfiltration or interstitial, tubular or FSGS lesions or foot process effacement. Conclusions.These studies dissociated systemic hypertension and proteinuria from the renal lesions in this model. Durable effects of losartan on blood pressure and proteinuria likely represent epigenetic processes.

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KW - focal segmental glomerulosclerosis

KW - hypertension

KW - interstitial fibrosis

KW - proteinuria

KW - renal ablation

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