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September 18, 2014PLoS ONE16 citationsOpen Access

Regression of Glomerular and Tubulointerstitial Injuries by Dietary Salt Reduction with Combination Therapy of Angiotensin II Receptor Blocker and Calcium Channel Blocker in Dahl Salt-Sensitive Rats

KRKazi RafiqANAkira NishiyamaYKYoshio Konishi

Key Result

Dietary salt reduction combined with an angiotensin II receptor blocker and a calcium channel blocker significantly reversed established high-salt diet-induced glomerular and tubulointerstitial injuries in Dahl salt-sensitive rats.

Structured PICO

Does dietary salt reduction combined with olmesartan and azelnidipine reverse established renal tissue injury in Dahl salt-sensitive hypertensive rats?

P
Population
Male Dahl salt-sensitive rats with high-salt diet-induced hypertension and renal injury, followed for up to 14 weeks.
I
Intervention
Dietary salt reduction (normal salt, 0.5% NaCl) plus combination therapy of olmesartan (10 mg/kg/day p.o.) and azelnidipine (3 mg/kg/day p.o.) for 10 weeks.
C
Comparator
Continued high-salt diet, normal-salt diet alone, normal-salt + olmesartan, normal-salt + azelnidipine, or normal-salt + hydralazine (50 mg/kg/day p.o.).
O
Outcome
Regression of renal tissue injury (glomerular and tubulointerstitial injuries), proteinuria, and systolic blood pressure.surrogate

In a rat model of salt-sensitive hypertension, dietary salt reduction combined with an ARB and a CCB reversed established glomerular and tubulointerstitial injuries.

Main Result

p-value: p=<0.05

Limitations

  • Did not evaluate blood pressure using a telemetry system
  • Unable to investigate changes in dipping pattern of blood pressure
  • Limited number of animals

Abstract

A growing body of evidence indicates that renal tissue injuries are reversible. We investigated whether dietary salt reduction with the combination therapy of angiotensin II type 1 receptor blocker (ARB) plus calcium channel blocker (CCB) reverses renal tissue injury in Dahl salt-sensitive (DSS) hypertensive rats. DSS rats were fed a high-salt diet (HS; 4% NaCl) for 4 weeks. Then, DSS rats were given one of the following for 10 weeks: HS diet; normal-salt diet (NS; 0.5% NaCl), NS + an ARB (olmesartan, 10 mg/kg/day), NS + a CCB (azelnidipine, 3 mg/kg/day), NS + olmesartan + azelnidipine or NS + hydralazine (50 mg/kg/day). Four weeks of treatment with HS diet induced hypertension, proteinuria, glomerular sclerosis and hypertrophy, glomerular podocyte injury, and tubulointerstitial fibrosis in DSS rats. A continued HS diet progressed hypertension, proteinuria and renal tissue injury, which was associated with inflammatory cell infiltration and increased proinflammatory cytokine mRNA levels, NADPH oxidase activity and NADPH oxidase-dependent superoxide production in the kidney. In contrast, switching to NS halted the progression of hypertension, renal glomerular and tubular injuries. Dietary salt reduction with ARB or with CCB treatment further reduced blood pressure and partially reversed renal tissues injury. Furthermore, dietary salt reduction with the combination of ARB plus CCB elicited a strong recovery from HS-induced renal tissue injury including the attenuation of inflammation and oxidative stress. These data support the hypothesis that dietary salt reduction with combination therapy of an ARB plus CCB restores glomerular and tubulointerstitial injury in DSS rats.

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Cite This Study

Rafiq et al. (2014) studied Salt-dependent hypertension and renal tissue injury. Dietary salt reduction with olmesartan and azelnidipine vs. High-salt diet (4% NaCl) or normal salt alone was evaluated on Regression of renal tissue injury (glomerular sclerosis and tubulointerstitial fibrosis) (p=<0.05). Dietary salt reduction combined with an angiotensin II receptor blocker and a calcium channel blocker significantly reversed established high-salt diet-induced glomerular and tubulointerstitial injuries in Dahl salt-sensitive rats.

synapsesocial.com/papers/6a82d40ec19603ede2440398https://doi.org/10.1371/journal.pone.0107853
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