Chisato Tojo

Publications (4)9.6 Total impact

• Article: Telmisartan inhibits vascular dysfunction and inflammation via activation of peroxisome proliferator-activated receptor-γ in subtotal nephrectomized rat.

  Hiroe Toba, Chisato Tojo, Jiahong Wang, Kazuki Noda, Miyuki Kobara, Tetsuo Nakata
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  ABSTRACT: Telmisartan, an angiotensin II type 1 receptor blocker, reportedly exhibits a partial peroxisome proliferator-activated receptor (PPAR)-γ agonistic action. To test whether telmisartan ameliorates vascular injury in the chronic kidney disease model rat through the PPAR-γ pathway, telmisartan (5 mg/kg per day, orally), losartan (5 mg/kg per day, orally) or telmisartan plus PPAR-γ antagonist, GW9662 (1 mg/kg/day, i.p.), was administered for 14 days to subtotal nephrectomized rats (Nx). There was no significant difference in systolic blood pressure or fasting blood glucose values among all groups. Subtotal nephrectomy significantly aggravated the levels of urinary protein excretion, blood urea nitrogen and plasma malondialdehyde concentration, which were attenuated by telmisartan or losartan treatment. Vasodilation in response to acetylcholine in the aortic ring was impaired in the Nx, and improved by treatment with telmisartan. Immunohistochemical analysis revealed that the infiltration of adventitial areas by macrophages and expression of osteopontin and vascular cell adhesion molecule-1 were enhanced in the Nx aorta and the overexpression was suppressed by telmisartan. The increased NADPH oxidase-derived superoxide production in the aorta from the Nx rat was suppressed by telmisartan. Cotreatment with GW9662 partly blunted the normalization of vascular dysfunction and inflammation. While losartan also attenuated these vascular changes in the Nx rats, the extent of the attenuation was significantly greater in the telmisartan-treated group than in the losartan-treated group. These results suggest that, in addition to a class effect of angiotensin II type 1 receptor blockers, telmisartan exerted vasoprotective effects through its PPAR-γ agonistic property in rats with renal failure.
  European journal of pharmacology 01/2012; 685(1-3):91-8. · 2.59 Impact Factor
• Article: Recombinant human erythropoietin ameliorated endothelial dysfunction and macrophage infiltration by increasing nitric oxide in hypertensive 5/6 nephrectomized rat aorta.

  Hiroe Toba, Masayuki Morishita, Chisato Tojo, Arisa Nakano, Yuko Oshima, Yushi Kojima, Mamiko Yoshida, Kohei Nakashima, Jiahong Wang, Miyuki Kobara, Tetsuo Nakata
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  ABSTRACT: Recombinant human erythropoietin (rHuEPO), used clinically for renal anemia, reportedly exhibits pleiotropic properties in various tissues. To test whether it ameliorates vascular injury, rHuEPO (75U/kg) was administered subcutaneously every 3days for 10days to 5/6 nephrectomized hypertensive rats (5/6Nx) treated with 1% NaCl. rHuEPO had no effect on increased systolic blood pressure or decreased hematocrit values, but normalized levels of proteinuria and creatinine clearance. Vasodilation in response to acetylcholine in the aortic ring was impaired in the 5/6Nx, and improved by treatment with rHuEPO. Immunohistochemical analysis revealed that the infiltration of adventitial areas by macrophages and expression of osteopontin were enhanced in the 5/6Nx aorta and the overexpression was suppressed by rHuEPO. rHuEPO also attenuated medial hyperplasia. Akt signaling was activated by the increased expression of phosphorylated Akt and GSK-3β in aorta from rHuEPO-treated 5/6Nx. rHuEPO restored plasma NOx (NO(2)(-)+NO(3)(-)) levels and endothelial nitric oxide synthase (eNOS) content in the 5/6Nx aorta. Treatment with an eNOS substrate, l-arginine, which caused a similar increase in plasma NOx levels as the rHuEPO treatment, resulted in a normalization of endothelial dysfunction and vascular inflammation. These results suggest that a low dose of rHuEPO exerted vasoprotective effects in rats with hypertensive renal failure.
  European journal of pharmacology 02/2011; 656(1-3):81-7. · 2.59 Impact Factor
• Article: L/N-type calcium channel blocker cilnidipine ameliorates proteinuria and inhibits the renal renin-angiotensin-aldosterone system in deoxycorticosterone acetate-salt hypertensive rats.

  Hiroe Toba, Mamiko Yoshida, Chisato Tojo, Arisa Nakano, Yuko Oshima, Yushi Kojima, Kazuki Noda, Jiahong Wang, Miyuki Kobara, Tetsuo Nakata
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  ABSTRACT: Cilnidipine, an N/L-type calcium channel blocker, has been reported to inhibit sympathetic nerve activity and has a greater renoprotective effect than L-type calcium channel blockers. To investigate the hypothesis that cilnidipine might ameliorate advanced hypertensive nephropathy and inhibit the renal renin-angiotensin-aldosterone system, cilnidipine (1 mg per kg per day) or amlodipine (1 mg per kg per day) was administered to uninephrectomized deoxycorticosterone (DOCA)-salt hypertensive rats (DOCA-salt) for 4 weeks by gavage. Although the blood pressure in the DOCA-salt group was higher than that of control, neither cilnidipine nor amlodipine had any effect on the increase in blood pressure in the DOCA-salt group. The DOCA (40 mg per kg per week, subcutaneously (s.c.)) and salt (1% NaCl in drinking water) treatment significantly aggravated the levels of urinary protein excretion and creatinine clearance and increased glomerulosclerosis and collagen deposition in the tubulointerstitial area of the kidney. These effects were attenuated by cilnidipine treatment. Reverse transcription-polymerase chain reaction analysis revealed that the renal expression of mRNA for collagen I/IV and transforming growth factor-β was enhanced in the DOCA-salt group and that the overexpression of these molecules was suppressed by cilnidipine. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived superoxide production in the kidney and urinary norepinephrine excretion, which were enhanced in the DOCA-salt group, were suppressed by cilnidipine. Cilnidipine also decreased the activity and expression of angiotensin-converting enzyme (ACE) and the aldosterone concentration in the renal homogenate. Although neither cilnidipine nor amlodipine had any effect on the increased blood pressure in the DOCA-salt group, these renal changes were not induced by treatment with amlodipine. In conclusion, cilnidipine inhibited renal dysfunction, sympathetic nerve activity and renal renin-angiotensin-aldosterone system in the DOCA-salt group.
  Hypertension Research 01/2011; 34(4):521-9. · 2.58 Impact Factor
• Article: Erythropoietin prevents vascular inflammation and oxidative stress in subtotal nephrectomized rat aorta beyond haematopoiesis.

  Hiroe Toba, Kohei Nakashima, Yuko Oshima, Yushi Kojima, Chisato Tojo, Arisa Nakano, Jiahong Wang, Miyuki Kobara, Tetsuo Nakata
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  ABSTRACT: 1. Recombinant human erythropoietin (rHuEPO) has been used for the management of renal anaemia. Recent studies suggest pleiotropic properties of rHuEPO in various tissues. The aim of the present study was to investigate the vasoprotective effects of rHuEPO in renal failure rats. 2. Rats subjected to 5/6 and 17/18 nephrectomy (5/6Nx and 17/18Nx rats, respectively) were treated with rHuEPO (75 U/kg, s.c.) three times a week for 2 weeks. 3. Administration of rHuEPO to 5/6Nx or 17/18Nx rats had no effect on systolic blood pressure or decreased haematocrit. However, rHuEPO treatment normalized proteinuria and creatinine clearance in 5/6Nx, but not in 17/18Nx, rats. 4. Vasodilation in response to acetylcholine in aortic rings was impaired in 5/6Nx and 17/18Nx rats and improved by rHuEPO in both groups. Immunohistochemical analysis revealed that macrophage infiltration into adventitial areas and the expression of osteopontin were enhanced in aortas from 5/6Nx and 17/18Nx rats, but that rHuEPO suppressed these effects. In addition, rHuEPO attenuated medial hyperplasia and NADPH oxidase-derived superoxide production in 5/6Nx and 17/18Nx rats. 5. Activation of the Akt signalling pathway was evident in rHuEPO-treated rats as the increased expression of phosphorylated Akt and glycogen synthase kinase-3β. Treatment with rHuEPO restored the expression of phosphorylated endothelial nitric oxide synthase in the aorta and urinary excretion of NO(x) in nephrectomized rats. 6. These results suggest that a low dose of rHuEPO results in the normalization of endothelial function, vascular inflammation and oxidative stress in rats with renal ablation beyond haematopoiesis. In addition, these vasoprotective effects are observed even in a state of deteriorating renal dysfunction.
  Clinical and Experimental Pharmacology and Physiology 12/2010; 37(12):1139-46. · 1.85 Impact Factor