Combination Therapy With Telmisartan and Spironolactone Alleviates L-NAME Exacerbated Nephrosclerosis With an Increase in PPAR-γ and Decrease in TGF-β1
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概要
- 論文の詳細を見る
To investigate whether the receptor blockades of angiotensin II type 1 and aldosterone receptors can prevent renal tissue injury in relation to the renal tissue mRNA levels of peroxisome proliferation-activated receptors-γ (PPAR-γ) and transforming growth factor-β 1 (TGF-β1) in spontaneously hypertensive rats (SHR) given NG-nitro-L-arginine methyl ester (L-NAME), which is considered a model of malignant hypertension. This study was performed in 5 groups of 17-week-old male SHR treated for 3 weeks as follows: group 1, control; group 2, L-NAME (50 mg/L in drinking); group 3, L-NAME plus aldosterone antagonist, spironolactone (SPRL, 100 mg/kg/day); group 4, L-NAME plus angiotensin II type 1 receptor blocker, telmisartan (TELM, 3 mg/kg/day); group 5, L-NAME plus combination therapy (COMB) with low-dose TELM (1 mg/kg/day) and SPRL (100 mg/kg/day). Urinary protein excretion and the glomerular injury score were significantly reduced in the SPRL, TELM, and COMB groups as compared with the L-NAME group, while significant blood pressure reduction was observed only in the TELM group. In the TELM and COMB groups, the perivascular cell infiltration and fibrosis area were significantly reduced together with the PPAR-γ mRNA increase and TGF- β1 mRNA decrease. The urinary excretion of nitric oxides was significantly recovered and the wall to lumen ratio of the interlobular artery was significantly reduced only in the COMB group compared with the L-NAME group. Combined administration of 1 mg/kg/day telmisartan and 100 mg/kg/day spironolactone is thought to be effective in alleviating hypertensive renal injuries independently of blood pressure changes. The anti-inflammatory and antifibrotic effects due to PPAR-γ activation and TGF-β1 inhibition may participate in the renoprotection of this combination therapy.
- インターナショナル・ハート・ジャーナル刊行会の論文
著者
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MATSUOKA Hiroaki
Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University, Mibu
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Matsuoka Hiroaki
獨協医科大学 循環器内科
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Ishimitsu Toshihiko
Department Of Hypertension And Cardiorenal Medicine Dokkyo Medical University
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ONO Hidehiko
Department of Cardiovascular Medicine, Hypertension and Cardiorenal Medicine, Dokkyo University Scho
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Takahashi Toshiaki
Department of Hypertension and Cardiorenal Disease, Dokkyo Medical University
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Ono Yuko
Department of Pathology, Dokkyo Medical University
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Ono Yuko
Department Of Geriatric And Environmental Dermatology Nagoya City University Graduate School Of Medi
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Takahashi Toshiaki
Department Of Anesthesiology Tokyo Medical University
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Matsuoka Hiroaki
Department Of Bioscience National Cardiovascular Center Research Institute
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Ishimitsu Toshihiko
Department of Cardiology and Nephrology, Dokkyo Medical University School of Medicine
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Ishimitsu Toshihiko
Department of Hypertension and Cardiorenal Disease, Dokkyo Medical University
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Ono Hidehiko
Department of Hypertension and Cardiorenal Disease, Dokkyo Medical University
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