Abstract | BACKGROUND: METHODS: Ten Munich-Wistar rats underwent 1½ surgical N; eight littermates were pretreated with losartan (L) only for 6 weeks prior to 1½ 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 1½ 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:
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Authors | Hye Won Park, Youngki Kim, Kee Hyuck Kim, Silvia Rozen, Behzad Najafian, Michael Mauer |
Journal | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
(Nephrol Dial Transplant)
Vol. 27
Issue 1
Pg. 107-14
(Jan 2012)
ISSN: 1460-2385 [Electronic] England |
PMID | 21633100
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiotensin II Type 1 Receptor Blockers
- Losartan
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Topics |
- Angiotensin II Type 1 Receptor Blockers
(pharmacology)
- Animals
- Glomerular Filtration Rate
- Hypertension
(etiology, prevention & control)
- Kidney Diseases
(etiology, prevention & control)
- Kidney Function Tests
- Losartan
(pharmacology)
- Male
- Nephrectomy
(adverse effects)
- Proteinuria
(etiology, prevention & control)
- Rats
- Rats, Wistar
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