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.

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.
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DOI:
10.1371/journal.pone.0107853
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Imanishi M
Imanishi M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Rafiq K;Nishiyama A;Konishi Y;Morikawa T;Kitabayashi C;Kohno M;Masaki T;Mori H;Kobori H;Imanishi M

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越来越多的证据表明,肾组织损伤是可逆的。我们研究了血管紧张素II型1受体阻滞剂(ARB)和钙通道阻滞剂(CCB)联合治疗饮食盐减少是否能逆转Dahl盐敏感(DSS)高血压大鼠肾组织损伤。DSS大鼠连续4周饲喂高盐日粮(HS; 4% NaCl)。然后,给DSS大鼠喂食以下方式之一,持续10周:HS饮食;正常盐饮食(NS; 0.5% NaCl), NS + ARB(奥美沙坦,10 mg/kg/天),NS + CCB(阿泽尔尼地平,3 mg/kg/天),NS +奥美沙坦+阿泽尔尼地平或NS +肼嗪(50 mg/kg/天)。用HS饮食治疗4周后,DSS大鼠出现高血压、蛋白尿、肾小球硬化和肥大、肾小球足细胞损伤和小管间质纤维化。持续高糖饮食会导致高血压、蛋白尿和肾组织损伤,这与炎症细胞浸润、促炎细胞因子mRNA水平、NADPH氧化酶活性和肾脏中NADPH氧化酶依赖性超氧化物的产生增加有关。相反,改用NS可阻止高血压、肾小球和肾小管损伤的进展。ARB或CCB治疗的饮食盐减少进一步降低血压并部分逆转肾组织损伤。此外,ARB + CCB联合减少饮食盐可以促进hs诱导的肾组织损伤的恢复,包括炎症和氧化应激的减弱。这些数据支持了膳食盐减少与ARB + CCB联合治疗可恢复DSS大鼠肾小球和小管间质损伤的假设。
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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