Comparison of the effects of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade on the evolution of spontaneous glomerular injury in male MWF/Ztm rats

Andrea Remuzzi, Barbara Malanchini, Cristina Battaglia, Tullio Bertani, Giuseppe Remuzzi

Research output: Contribution to journalArticle

Abstract

The mechanism by which angiotensin-converting enzyme (ACE) inhibitors prevent proteinuria and glomerulosclerosis in experimental nephropathies is not yet clear. Experimental evidence is available that the effect of ACE inhibitors on the glomerular function depends on the inhibition of angiotensin II generation, but it is possible that inhibition of the bradykinin breakdown also plays a relevant role. To establish the mediators of the effect of ACE inhibitors in glomerular injury, we compared the effects of the ACE inhibitor lisinopril with those of a specific angiotensin receptor (AT1) antagonist (ZD7155) on the renal function in male MWF/Ztm rats. After 4 months (end of the study), the untreated animals developed hypertension and proteinuria ( 160 ± 10 mm Hg and 214 ± 92 mg/24 h, respectively). In the lisinopril- and in the ZD7155-treated rats, a comparable systolic pressure control was achieved (121 ± 12 and 118 ± 14 mm Hg) respectively), and proteinuria was significantly prevented (averaging only 38 ± 23 and 30 ± 8 mg/24 h, respectively) at the end of the study. The glomerular filtration rate was comparable in control and lisinopril-treated rats and significantly increased in ZD7155-treated rats. Both treatments significantly reduced the glomerular capillary pressure and significantly increased the ultrafiltration coefficient (K(f)) as compared with untreated animals. In ZD7155-treated rats the K(f) was also significantly higher than in lisinopril-treated rats. Morphological analysis of kidney tissue revealed that in untreated animals glomerular sclerosis and tubulointerstitital damage developed. Structural changes were absent in lisinopril- and ZD7155-treated animals. These results show that the antihypertensive and renal protective effects of ACE inhibitors are shared by the angiotensin receptor antagonist. Thus, angiotensin II is the likely mediator of proteinuria and glomerulosclerosis which develop spontaneously with age in this model.

Original languageEnglish
Pages (from-to)19-25
Number of pages7
JournalExperimental Nephrology
Volume4
Issue number1
Publication statusPublished - 1996

Fingerprint

Angiotensin Receptors
Lisinopril
Peptidyl-Dipeptidase A
Angiotensin-Converting Enzyme Inhibitors
Proteinuria
Wounds and Injuries
Angiotensin Receptor Antagonists
Kidney
Angiotensin II
Ultrafiltration
Bradykinin
Sclerosis
Glomerular Filtration Rate
Antihypertensive Agents
ZD 7155
Blood Pressure
Hypertension
Pressure

Keywords

  • Angiotensin
  • Angiotensin receptor antagonist
  • Angiotensin-converting enzyme
  • MWF/Ztm
  • Proteinuria
  • Renal hemodynamics

ASJC Scopus subject areas

  • Nephrology

Cite this

Comparison of the effects of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade on the evolution of spontaneous glomerular injury in male MWF/Ztm rats. / Remuzzi, Andrea; Malanchini, Barbara; Battaglia, Cristina; Bertani, Tullio; Remuzzi, Giuseppe.

In: Experimental Nephrology, Vol. 4, No. 1, 1996, p. 19-25.

Research output: Contribution to journalArticle

@article{f5fa14fd788c42a99a3cb121e43e50aa,
title = "Comparison of the effects of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade on the evolution of spontaneous glomerular injury in male MWF/Ztm rats",
abstract = "The mechanism by which angiotensin-converting enzyme (ACE) inhibitors prevent proteinuria and glomerulosclerosis in experimental nephropathies is not yet clear. Experimental evidence is available that the effect of ACE inhibitors on the glomerular function depends on the inhibition of angiotensin II generation, but it is possible that inhibition of the bradykinin breakdown also plays a relevant role. To establish the mediators of the effect of ACE inhibitors in glomerular injury, we compared the effects of the ACE inhibitor lisinopril with those of a specific angiotensin receptor (AT1) antagonist (ZD7155) on the renal function in male MWF/Ztm rats. After 4 months (end of the study), the untreated animals developed hypertension and proteinuria ( 160 ± 10 mm Hg and 214 ± 92 mg/24 h, respectively). In the lisinopril- and in the ZD7155-treated rats, a comparable systolic pressure control was achieved (121 ± 12 and 118 ± 14 mm Hg) respectively), and proteinuria was significantly prevented (averaging only 38 ± 23 and 30 ± 8 mg/24 h, respectively) at the end of the study. The glomerular filtration rate was comparable in control and lisinopril-treated rats and significantly increased in ZD7155-treated rats. Both treatments significantly reduced the glomerular capillary pressure and significantly increased the ultrafiltration coefficient (K(f)) as compared with untreated animals. In ZD7155-treated rats the K(f) was also significantly higher than in lisinopril-treated rats. Morphological analysis of kidney tissue revealed that in untreated animals glomerular sclerosis and tubulointerstitital damage developed. Structural changes were absent in lisinopril- and ZD7155-treated animals. These results show that the antihypertensive and renal protective effects of ACE inhibitors are shared by the angiotensin receptor antagonist. Thus, angiotensin II is the likely mediator of proteinuria and glomerulosclerosis which develop spontaneously with age in this model.",
keywords = "Angiotensin, Angiotensin receptor antagonist, Angiotensin-converting enzyme, MWF/Ztm, Proteinuria, Renal hemodynamics",
author = "Andrea Remuzzi and Barbara Malanchini and Cristina Battaglia and Tullio Bertani and Giuseppe Remuzzi",
year = "1996",
language = "English",
volume = "4",
pages = "19--25",
journal = "Experimental Nephrology",
issn = "1018-7782",
publisher = "S. Karger AG",
number = "1",

}

TY - JOUR

T1 - Comparison of the effects of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade on the evolution of spontaneous glomerular injury in male MWF/Ztm rats

AU - Remuzzi, Andrea

AU - Malanchini, Barbara

AU - Battaglia, Cristina

AU - Bertani, Tullio

AU - Remuzzi, Giuseppe

PY - 1996

Y1 - 1996

N2 - The mechanism by which angiotensin-converting enzyme (ACE) inhibitors prevent proteinuria and glomerulosclerosis in experimental nephropathies is not yet clear. Experimental evidence is available that the effect of ACE inhibitors on the glomerular function depends on the inhibition of angiotensin II generation, but it is possible that inhibition of the bradykinin breakdown also plays a relevant role. To establish the mediators of the effect of ACE inhibitors in glomerular injury, we compared the effects of the ACE inhibitor lisinopril with those of a specific angiotensin receptor (AT1) antagonist (ZD7155) on the renal function in male MWF/Ztm rats. After 4 months (end of the study), the untreated animals developed hypertension and proteinuria ( 160 ± 10 mm Hg and 214 ± 92 mg/24 h, respectively). In the lisinopril- and in the ZD7155-treated rats, a comparable systolic pressure control was achieved (121 ± 12 and 118 ± 14 mm Hg) respectively), and proteinuria was significantly prevented (averaging only 38 ± 23 and 30 ± 8 mg/24 h, respectively) at the end of the study. The glomerular filtration rate was comparable in control and lisinopril-treated rats and significantly increased in ZD7155-treated rats. Both treatments significantly reduced the glomerular capillary pressure and significantly increased the ultrafiltration coefficient (K(f)) as compared with untreated animals. In ZD7155-treated rats the K(f) was also significantly higher than in lisinopril-treated rats. Morphological analysis of kidney tissue revealed that in untreated animals glomerular sclerosis and tubulointerstitital damage developed. Structural changes were absent in lisinopril- and ZD7155-treated animals. These results show that the antihypertensive and renal protective effects of ACE inhibitors are shared by the angiotensin receptor antagonist. Thus, angiotensin II is the likely mediator of proteinuria and glomerulosclerosis which develop spontaneously with age in this model.

AB - The mechanism by which angiotensin-converting enzyme (ACE) inhibitors prevent proteinuria and glomerulosclerosis in experimental nephropathies is not yet clear. Experimental evidence is available that the effect of ACE inhibitors on the glomerular function depends on the inhibition of angiotensin II generation, but it is possible that inhibition of the bradykinin breakdown also plays a relevant role. To establish the mediators of the effect of ACE inhibitors in glomerular injury, we compared the effects of the ACE inhibitor lisinopril with those of a specific angiotensin receptor (AT1) antagonist (ZD7155) on the renal function in male MWF/Ztm rats. After 4 months (end of the study), the untreated animals developed hypertension and proteinuria ( 160 ± 10 mm Hg and 214 ± 92 mg/24 h, respectively). In the lisinopril- and in the ZD7155-treated rats, a comparable systolic pressure control was achieved (121 ± 12 and 118 ± 14 mm Hg) respectively), and proteinuria was significantly prevented (averaging only 38 ± 23 and 30 ± 8 mg/24 h, respectively) at the end of the study. The glomerular filtration rate was comparable in control and lisinopril-treated rats and significantly increased in ZD7155-treated rats. Both treatments significantly reduced the glomerular capillary pressure and significantly increased the ultrafiltration coefficient (K(f)) as compared with untreated animals. In ZD7155-treated rats the K(f) was also significantly higher than in lisinopril-treated rats. Morphological analysis of kidney tissue revealed that in untreated animals glomerular sclerosis and tubulointerstitital damage developed. Structural changes were absent in lisinopril- and ZD7155-treated animals. These results show that the antihypertensive and renal protective effects of ACE inhibitors are shared by the angiotensin receptor antagonist. Thus, angiotensin II is the likely mediator of proteinuria and glomerulosclerosis which develop spontaneously with age in this model.

KW - Angiotensin

KW - Angiotensin receptor antagonist

KW - Angiotensin-converting enzyme

KW - MWF/Ztm

KW - Proteinuria

KW - Renal hemodynamics

UR - http://www.scopus.com/inward/record.url?scp=0030071327&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030071327&partnerID=8YFLogxK

M3 - Article

C2 - 8788596

AN - SCOPUS:0030071327

VL - 4

SP - 19

EP - 25

JO - Experimental Nephrology

JF - Experimental Nephrology

SN - 1018-7782

IS - 1

ER -