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Publications (7)11.82 Total impact

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    ABSTRACT: We examined the effects of the angiotensin II type 1 receptor blocker candesartan, the calcium channel blockers benidipine and amlodipine, hydralazine, and the combination of candesartan and benidipine or amlodipine on blood pressure and renal function in Dahl salt-sensitive (DS) hypertensive rats. Male DS rats (5 weeks of age) were fed a high-salt (8% NaCl) diet, resulting in hypertension accompanied by glomerular sclerosis and an increased urinary albumin excretion. Drugs were orally administered from 2 to 6 weeks after the start of the feeding. Although candesartan (1 or 10 mg/kg) had little effect on the blood pressure, benidipine (4 mg/kg), amlodipine (4 mg/kg) and hydralazine (5 mg/kg) had similar hypotensive effects. Benidipine, but not amlodipine, hydralazine, or candesartan, significantly inhibited the increase in the albuminuria and glomerular sclerosis. The combination of candesartan (1 mg/kg) and benidipine (4 mg/kg) lowered the levels of blood pressure and albuminuria more effectively than the combination of candesartan (1 mg/kg) and amlodipine (4 mg/kg). These results indicate that benidipine is effective in preventing the impairment of renal function in DS hypertensive rats, and suggest that additional benefits can be expected by combination therapy with benidipine and an angiotensin II type 1 receptor blocker.
    Hypertension Research 08/2003; 26(8):635-41. · 2.79 Impact Factor
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    ABSTRACT: We examined the effect of the dihydropyridine calcium channel blocker (CCB) benidipine, the angiotensin II type 1 receptor blocker (ARB) candesartan, and the combination of these drugs on blood pressure and kidney and vascular function in rats with salt-induced hypertension. Dahl salt-sensitive (DS) rats were fed with a high-salt (8% NaCl) diet from 7 weeks of age. Benidipine (1, 3 mg/kg), candesartan (1, 3 mg/kg), benidipine (3 mg/kg) combined with candesartan (3 mg/kg), or vehicle was administered orally after the start of the feeding. Relaxant responses to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) were measured to examine the vascular function. DS rats fed the high-salt diet showed an increase in systolic blood pressure (SBP), which was accompanied by glomerular sclerosis and an increase in urinary albumin excretion. Relaxant responses to acetylcholine and sodium nitroprusside were impaired in superior mesenteric arterial rings from the hypertensive DS rats. SBP was significantly lower in all of the drug-treated groups than in the vehicle-treated group. The antihypertensive effect of benidipine at 3 mg/kg was more potent than that of candesartan at 3 mg/kg. The albuminuria was significantly decreased in the benidipine and benidipine plus candesartan groups, but not in the candesartan group. The level of SBP in the benidipine plus candesartan group was lower than that by either drug alone. In addition, benidipine alone and benidipine plus candesartan inhibited the glomerular sclerosis and the impairment of relaxant responses in the arteries. These results demonstrate that benidipine is more effective than candesartan in lowering blood pressure and preventing the impairment of kidney and vascular function in salt-sensitive hypertensive rats. In addition, the results suggest that combination therapy with benidipine and an ARB decreases blood pressure more effectively than either drug alone and may be useful for the treatment of hypertension.
    Hypertension Research 08/2003; 26(7):569-76. · 2.79 Impact Factor
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    ABSTRACT: The protective effects of glutathione (GSH) administration on myelosuppression induced by 5-fluorouracil (5-FU) were investigated in female BALB/c mice. Animals were allocated to four groups (16 mice/group). GSH was given orally at a dose of 800 mg/kg to groups 3 and 4 for 21 consecutive days (day 0 to day 20). 5-FU was repeatedly administered at a dose of 40 mg/kg to groups 2 and 3 for 1 week (day 7 to day 13) by gavage. Group 3 served as a combined treatment group and group 1 as a non-treated control group. The total observation period was 3 weeks. Body weight was measured once a week. A decrease in body weight due to 5-FU treatment was observed in groups 2 and 3 on day 14. Although the body weight in group 2 had not increased by 1-week after cessation of 5-FU treatment, the value in group 3 markedly recovered. Hematology, total nucleated myelocyte count and histopathology of bone marrow were carried out on day 14 and day 21. In groups 2 and 3, these examinations showed thrombocytopenia, leukopenia, reticulocytopenia and myelosuppression on day 14. However, platelets and bone marrow were less affected in group 3 than in group 2. On day 21, the thrombocytopenia in groups 2 and 3 was resolved. The myelosuppression, leukopenia and reticulocytopenia resolved in group 3, but not in group 2. Although simple microcytic anemia occurred delayed on day 21, it was less severe in group 3 than in group 2. Therefore, GSH may have preventive effects against 5-FU-induced hematopoietic toxicity, and accelerate recovery after cessation of 5-FU treatment.
    Archive für Toxikologie 06/2003; 77(5):285-90. · 5.22 Impact Factor
  • Journal of Toxicologic Pathology 01/2003; 16(3):187-190. · 0.34 Impact Factor
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    ABSTRACT: Background: Olopatadine hydrochloride is an anti-allergic agent with histamine H1 receptor antagonistic action. We investigated the effects of olopatadine on passive anaphylaxis reaction- and compound 48/80-induced conjunctivitis in rats.Methods: Allergic conjunctivitis was induced in rats passively sensitized by injection of rat anti-ovalbumin (anti-OVA) serum into the upper subconjunctiva of the right eye, followed by intravenous administration of the antigen and Evans blue dye. After 30 min, the amount of dye leaking into the conjunctiva was measured. Non-allergic conjunctivitis was induced in rats by injection of compound 48/80. Olopatadine or other reference compounds were orally given 1 h before the challenge.Results: The amount of dye leaking into the ­conjunctiva following passive anaphylaxis was ­significantly inhibited by oral administration of 0.01−1 mg/kg olopatadine and the ID50 value was 0.093 mg/kg. In the control group, pathological examination revealed edema and lymphocyte infiltration in the conjunctiva and the pal­pebral skin. Olopatadine, at 0.03 and 0.3 mg/kg, reduced the grade of these pathological findings. The other antiallergic drugs (1 mg/kg loratadine, 0.3 mg/kg epinastine, 0.3 mg/kg cetiridine, 1 mg/kg ebastine, 30 mg/kg fexofenadine and 3 mg/kg chlorpheniramine), when administered orally, inhibited the passive anaphylaxis reaction-induced vascular hyperpermeability of the conjunctiva, as was the case with olopatadine hydrochloride. Subconjunctival administration of compound 48/80 induced vascular hyper­permeability, which is presumably mediated by histamine release. Oral administration of 0.1 and 1 mg/kg olopatadine significantly inhibited the amount of dye leakage.Conclusion: Orally administered olopatadine is expected to improve allergic conjunctivitis.
    Allergology International 01/2003; 52(2):77-83.
  • Journal of Toxicologic Pathology 01/2001; 14(3):225-230. · 0.34 Impact Factor
  • Journal of Toxicologic Pathology 01/2001; 14(3):179-186. · 0.34 Impact Factor