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Titolo:
INFLUENCE OF SPECIFIC AND NONSPECIFIC ENDOTHELIN RECEPTOR ANTAGONISTSON RENAL MORPHOLOGY IN RATS WITH SURGICAL RENAL ABLATION
Autore:
NABOKOV A; AMANN K; WAGNER J; GEHLEN F; MUNTER K; RITZ E;
Indirizzi:
UNIV HEIDELBERG,DEPT INTERNAL MED,BERGHEIMER STR 56A D-69115 HEIDELBERG GERMANY UNIV HEIDELBERG,DEPT PATHOL D-69115 HEIDELBERG GERMANY KNOLL AG W-6700 LUDWIGSHAFEN GERMANY
Titolo Testata:
Nephrology, dialysis, transplantation
fascicolo: 3, volume: 11, anno: 1996,
pagine: 514 - 520
SICI:
0931-0509(1996)11:3<514:IOSANE>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
DISEASE PROGRESSION; GENE-EXPRESSION; REMNANT KIDNEY; NEPHRECTOMY; EXCRETION; INJURY; GROWTH;
Keywords:
GLOMERULAR HYPERTROPHY; GLOMERULOSCLEROSIS; ENDOTHELIN RECEPTOR ANTAGONIST; RENAL FAILURE; SUBTOTAL NEPHRECTOMY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
A. Nabokov et al., "INFLUENCE OF SPECIFIC AND NONSPECIFIC ENDOTHELIN RECEPTOR ANTAGONISTSON RENAL MORPHOLOGY IN RATS WITH SURGICAL RENAL ABLATION", Nephrology, dialysis, transplantation, 11(3), 1996, pp. 514-520

Abstract

Background. Studies in experimental models of chronic renal failure suggest an important role for the endothelin system in the development of renal scarring. Endothelin receptor (ETR) anatagonists interfere with progression, but it has not been resolved (i) whether this is true for all models of renal damage, (ii) to what extent the effect is modulated by systemic blood pressure and (iii) whether the effect is similar for ET(A)R and ET(A)/ET(B)R antagonists. Study design. 5/6 subtotalnephrectomy (SNX) by surgical ablation in male Sprague-Dawley rats. Comparison of ACE inhibitor Trandolapril (0.1 mg/kg/day), ET(A)R antagonist BMS 182874 (30 mg/kg/day) and ET(A)R/ET(B)R antagonist Ro 46-2005(30 mg/kg/day) by gavage. Duration of the experiment eight weeks. Methods. Systolic blood pressure by tail plethysmography. Perfusion fixation of kidneys and morphometric analysis ET-1 and ET(A)/ET(B)R by quantitative PCR.Results. SNX caused a significant (P < 0.01) increase of systolic blood pressure (170 +/- 8.6 mmHg) compared to sham operated controls (131 +/- 5.3 mmHg). Blood pressure was significantly (P < 0.001) lower with Trandolapril (128 +/- 5.3 mmHg), but not with EMS 182874(153 +/- 5.9 mmHg) or Ro 46-2005 (167 +/- 7.6 mmHg). Compared to shamoperated rats (0.03 +/- 0.01) glomerulosclerosis index (GSI) was significantly (P < 0.01) higher in the untreated SNX group (0.9 +/- 0.15). Significantly lower GSI was found in Trandolapril treated (0.29 +/- 0.04), EMS 182874 treated (0.36 +/- 0.05), and Ro 46-2005 treated animals (0.45 +/- 0.11). The effect of EMS 182874 was accompanied by lower tubulointerstitial damage index. Mean glomerular volume was dramatically increased (P < 0.001) in SNX rats as compared to sham operated animals. This glomerular enlargement was partially prevented by Trandolapril (P < 0.05), but not by either ETR antagonist. ET-1 mRNA tended to be higher in SNX irrespective of treatment, while ET(A)R and ET(B)R mRNA were significantly lower. Conclusion. Both specific (ET(A)R) and non-specific (ET(A)/ET(B)R) endothelin antagonists interfere with development of glomerulosclerosis by mechanisms which are, at least in part, independent of systemic blood pressure.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 10:44:31