Combined effects of losartan and pravastatin on interstitial inflammation and fibrosis in chronic cyclosporine-induced nephropathy

Can Li, Bo Kyung Sun, Sun Woo Lim, Joan Chang Song, Shin Wook Kang, Yu Seun Kim, Duk Hee Kang, Jung Ho Cha, Jin Kim, Chul Woo Yang

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background. Statins and angiotensin II type I receptor blockers have synergistic effects on vascular smooth-muscle-cell proliferation and the progression of renal diseases. We evaluated whether combined treatment with losartan (LSRT) and pravastatin (PRVT) affords superior protection compared with their respective monotherapies in treating chronic cyclosporine (CsA)-induced nephropathy in rats. Methods. Rats maintained on a low salt diet were given vehicle, CsA (15 mg/kg), CsA and LSRT (10 mg/kg), CsA and PRVT (5 mg/kg), or a combination of CsA, LSRT, and PRVT for 28 days. Basic parameters (renal function, systolic blood pressure, serum high-sensitivity C-reactive protein [hs-CRP], and lipid profiles), histopathology (arteriolopathy, tubulointerstitial fibrosis, and inflammatory cell infiltration), and inflammatory and fibrotic factors (intrarenal CRP, angiotensin II, osteopontin, and transforming growth factor [TGF]-β1) were studied. Results. LSRT or PRVT treatment significantly attenuated the histopathologic changes induced by CsA, and combined treatment with LSRT and PRVT further decreased these parameters compared with giving each drug alone. Increased levels of angiotensin II, intrarenal CRP, osteopontin, and TGF-β1 in CsA-treated rat kidney were reduced by treatment with either LSRT or PRVT and were further decreased by the combination of the two drugs. There were no significant differences in systolic blood pressure or serum lipid parameters between groups. Conclusions. Combined treatment with LSRT and PRVT provided synergistic effects in attenuating inflammatory and fibrotic processes in a rat model of chronic CsA-induced nephropathy, and this effect was independent of their hypolipidemic and hypotensive actions.

Original languageEnglish
Pages (from-to)1522-1529
Number of pages8
JournalTransplantation
Volume79
Issue number11
DOIs
Publication statusPublished - 2005 Jun 15

Fingerprint

Pravastatin
Losartan
Cyclosporine
Fibrosis
Inflammation
Blood Pressure
Osteopontin
Transforming Growth Factors
Kidney
Angiotensin II
Sodium-Restricted Diet
Lipids
Therapeutics
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Angiotensin I
Angiotensin Receptor Antagonists
Drug Combinations
Serum
Vascular Smooth Muscle
C-Reactive Protein

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Li, Can ; Sun, Bo Kyung ; Lim, Sun Woo ; Song, Joan Chang ; Kang, Shin Wook ; Kim, Yu Seun ; Kang, Duk Hee ; Cha, Jung Ho ; Kim, Jin ; Yang, Chul Woo. / Combined effects of losartan and pravastatin on interstitial inflammation and fibrosis in chronic cyclosporine-induced nephropathy. In: Transplantation. 2005 ; Vol. 79, No. 11. pp. 1522-1529.
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abstract = "Background. Statins and angiotensin II type I receptor blockers have synergistic effects on vascular smooth-muscle-cell proliferation and the progression of renal diseases. We evaluated whether combined treatment with losartan (LSRT) and pravastatin (PRVT) affords superior protection compared with their respective monotherapies in treating chronic cyclosporine (CsA)-induced nephropathy in rats. Methods. Rats maintained on a low salt diet were given vehicle, CsA (15 mg/kg), CsA and LSRT (10 mg/kg), CsA and PRVT (5 mg/kg), or a combination of CsA, LSRT, and PRVT for 28 days. Basic parameters (renal function, systolic blood pressure, serum high-sensitivity C-reactive protein [hs-CRP], and lipid profiles), histopathology (arteriolopathy, tubulointerstitial fibrosis, and inflammatory cell infiltration), and inflammatory and fibrotic factors (intrarenal CRP, angiotensin II, osteopontin, and transforming growth factor [TGF]-β1) were studied. Results. LSRT or PRVT treatment significantly attenuated the histopathologic changes induced by CsA, and combined treatment with LSRT and PRVT further decreased these parameters compared with giving each drug alone. Increased levels of angiotensin II, intrarenal CRP, osteopontin, and TGF-β1 in CsA-treated rat kidney were reduced by treatment with either LSRT or PRVT and were further decreased by the combination of the two drugs. There were no significant differences in systolic blood pressure or serum lipid parameters between groups. Conclusions. Combined treatment with LSRT and PRVT provided synergistic effects in attenuating inflammatory and fibrotic processes in a rat model of chronic CsA-induced nephropathy, and this effect was independent of their hypolipidemic and hypotensive actions.",
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Combined effects of losartan and pravastatin on interstitial inflammation and fibrosis in chronic cyclosporine-induced nephropathy. / Li, Can; Sun, Bo Kyung; Lim, Sun Woo; Song, Joan Chang; Kang, Shin Wook; Kim, Yu Seun; Kang, Duk Hee; Cha, Jung Ho; Kim, Jin; Yang, Chul Woo.

In: Transplantation, Vol. 79, No. 11, 15.06.2005, p. 1522-1529.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Combined effects of losartan and pravastatin on interstitial inflammation and fibrosis in chronic cyclosporine-induced nephropathy

AU - Li, Can

AU - Sun, Bo Kyung

AU - Lim, Sun Woo

AU - Song, Joan Chang

AU - Kang, Shin Wook

AU - Kim, Yu Seun

AU - Kang, Duk Hee

AU - Cha, Jung Ho

AU - Kim, Jin

AU - Yang, Chul Woo

PY - 2005/6/15

Y1 - 2005/6/15

N2 - Background. Statins and angiotensin II type I receptor blockers have synergistic effects on vascular smooth-muscle-cell proliferation and the progression of renal diseases. We evaluated whether combined treatment with losartan (LSRT) and pravastatin (PRVT) affords superior protection compared with their respective monotherapies in treating chronic cyclosporine (CsA)-induced nephropathy in rats. Methods. Rats maintained on a low salt diet were given vehicle, CsA (15 mg/kg), CsA and LSRT (10 mg/kg), CsA and PRVT (5 mg/kg), or a combination of CsA, LSRT, and PRVT for 28 days. Basic parameters (renal function, systolic blood pressure, serum high-sensitivity C-reactive protein [hs-CRP], and lipid profiles), histopathology (arteriolopathy, tubulointerstitial fibrosis, and inflammatory cell infiltration), and inflammatory and fibrotic factors (intrarenal CRP, angiotensin II, osteopontin, and transforming growth factor [TGF]-β1) were studied. Results. LSRT or PRVT treatment significantly attenuated the histopathologic changes induced by CsA, and combined treatment with LSRT and PRVT further decreased these parameters compared with giving each drug alone. Increased levels of angiotensin II, intrarenal CRP, osteopontin, and TGF-β1 in CsA-treated rat kidney were reduced by treatment with either LSRT or PRVT and were further decreased by the combination of the two drugs. There were no significant differences in systolic blood pressure or serum lipid parameters between groups. Conclusions. Combined treatment with LSRT and PRVT provided synergistic effects in attenuating inflammatory and fibrotic processes in a rat model of chronic CsA-induced nephropathy, and this effect was independent of their hypolipidemic and hypotensive actions.

AB - Background. Statins and angiotensin II type I receptor blockers have synergistic effects on vascular smooth-muscle-cell proliferation and the progression of renal diseases. We evaluated whether combined treatment with losartan (LSRT) and pravastatin (PRVT) affords superior protection compared with their respective monotherapies in treating chronic cyclosporine (CsA)-induced nephropathy in rats. Methods. Rats maintained on a low salt diet were given vehicle, CsA (15 mg/kg), CsA and LSRT (10 mg/kg), CsA and PRVT (5 mg/kg), or a combination of CsA, LSRT, and PRVT for 28 days. Basic parameters (renal function, systolic blood pressure, serum high-sensitivity C-reactive protein [hs-CRP], and lipid profiles), histopathology (arteriolopathy, tubulointerstitial fibrosis, and inflammatory cell infiltration), and inflammatory and fibrotic factors (intrarenal CRP, angiotensin II, osteopontin, and transforming growth factor [TGF]-β1) were studied. Results. LSRT or PRVT treatment significantly attenuated the histopathologic changes induced by CsA, and combined treatment with LSRT and PRVT further decreased these parameters compared with giving each drug alone. Increased levels of angiotensin II, intrarenal CRP, osteopontin, and TGF-β1 in CsA-treated rat kidney were reduced by treatment with either LSRT or PRVT and were further decreased by the combination of the two drugs. There were no significant differences in systolic blood pressure or serum lipid parameters between groups. Conclusions. Combined treatment with LSRT and PRVT provided synergistic effects in attenuating inflammatory and fibrotic processes in a rat model of chronic CsA-induced nephropathy, and this effect was independent of their hypolipidemic and hypotensive actions.

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