Adjunctive therapy with statins reduces residual albuminuria/proteinuria and provides further renoprotection by downregulating the angiotensin II-AT1 pathway in hypertensive nephropathy

Blockade of the renin-angiotensin II (Ang II) system by AT1 blockers (ARBs) and angiotensin-converting enzyme inhibitors retards the progression of chronic kidney disease (CKD) by reducing albuminuria/proteinuria. However, many patients with CKD suffer from residual albuminuria/proteinuria, which is...

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Veröffentlicht in:Journal of hypertension 2017-07, Vol.35 (7), p.1442-1456
Hauptverfasser: Zhang, Zhi, Li, Ziqiang, Cao, Kaijin, Fang, Dailong, Wang, Fazhan, Bi, Gang, Yang, Jian, He, Yingju, Wu, Jinhui, Wei, Yuquan, Song, Xiangrong
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container_end_page 1456
container_issue 7
container_start_page 1442
container_title Journal of hypertension
container_volume 35
creator Zhang, Zhi
Li, Ziqiang
Cao, Kaijin
Fang, Dailong
Wang, Fazhan
Bi, Gang
Yang, Jian
He, Yingju
Wu, Jinhui
Wei, Yuquan
Song, Xiangrong
description Blockade of the renin-angiotensin II (Ang II) system by AT1 blockers (ARBs) and angiotensin-converting enzyme inhibitors retards the progression of chronic kidney disease (CKD) by reducing albuminuria/proteinuria. However, many patients with CKD suffer from residual albuminuria/proteinuria, which is an independent risk factor for CKD progression. The aim of the current study is to investigate the effect of pitavastatin, one of the adjunctive agents to ARBs, on the reduction of albuminuria/proteinuria and further renoprotection mediated by telmisartan in spontaneously hypertensive rats. Forty-two-week-old spontaneously hypertensive rats were grouped randomly and received 8 weeks of treatments with vehicle, telmisartan, pitavastatin or a combination of telmisartan and pitavastatin. Both albuminuria and proteinuria were inhibited significantly in the telmisartan-treated group, but an obviously residual albuminuria was maintained. The combination treatment with telmisartan and pitavastatin displayed a more effective decrease in albuminuria and proteinuria, even to the normal level. Enhanced nephroprotection was also observed in this combination group, which was independent of the cholesterol-lowering effects. Further mechanistic studies revealed that the combination therapy greatly attenuated the expression of intrarenal Ang II and AT1, thereby decreasing the activation of TGF-β-Smad and NF-κB and inhibiting fibrosis and inflammation. Adjunctive therapy with pitavastatin dramatically reduced residual albuminuria/proteinuria and enhanced nephroprotection, likely by downregulating the expression of intrarenal Ang II and AT1. It could be concluded that statins might be a promising adjunctive therapeutic agent to conventional ARB treatment in hypertensive renal damage.
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Enhanced nephroprotection was also observed in this combination group, which was independent of the cholesterol-lowering effects. Further mechanistic studies revealed that the combination therapy greatly attenuated the expression of intrarenal Ang II and AT1, thereby decreasing the activation of TGF-β-Smad and NF-κB and inhibiting fibrosis and inflammation. Adjunctive therapy with pitavastatin dramatically reduced residual albuminuria/proteinuria and enhanced nephroprotection, likely by downregulating the expression of intrarenal Ang II and AT1. 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Enhanced nephroprotection was also observed in this combination group, which was independent of the cholesterol-lowering effects. Further mechanistic studies revealed that the combination therapy greatly attenuated the expression of intrarenal Ang II and AT1, thereby decreasing the activation of TGF-β-Smad and NF-κB and inhibiting fibrosis and inflammation. Adjunctive therapy with pitavastatin dramatically reduced residual albuminuria/proteinuria and enhanced nephroprotection, likely by downregulating the expression of intrarenal Ang II and AT1. It could be concluded that statins might be a promising adjunctive therapeutic agent to conventional ARB treatment in hypertensive renal damage.</abstract><cop>England</cop><pmid>28244896</pmid><doi>10.1097/HJH.0000000000001325</doi><tpages>15</tpages></addata></record>
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subjects Albuminuria - drug therapy
Albuminuria - metabolism
Angiotensin II - metabolism
Angiotensin II Type 1 Receptor Blockers - pharmacology
Angiotensin II Type 1 Receptor Blockers - therapeutic use
Angiotensin-Converting Enzyme Inhibitors - pharmacology
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Animals
Benzimidazoles - pharmacology
Benzimidazoles - therapeutic use
Benzoates - pharmacology
Benzoates - therapeutic use
Down-Regulation - drug effects
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Hypertension, Renal - drug therapy
Hypertension, Renal - metabolism
Kidney - drug effects
Kidney - metabolism
Male
Nephritis - drug therapy
Nephritis - metabolism
NF-kappa B - metabolism
Proteinuria - drug therapy
Rats
Rats, Inbred SHR
Receptor, Angiotensin, Type 1 - metabolism
Renin-Angiotensin System - drug effects
Signal Transduction - drug effects
Transforming Growth Factor beta - metabolism
title Adjunctive therapy with statins reduces residual albuminuria/proteinuria and provides further renoprotection by downregulating the angiotensin II-AT1 pathway in hypertensive nephropathy
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