Publications (2)9.75 Total impact
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Article: A 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor reduces hypertensive nephrosclerosis in stroke-prone spontaneously hypertensive rats.
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ABSTRACT: Recent studies suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors (statins) exert their protective effects against cardiovascular diseases independently of their cholesterol-decreasing effects. To clarify the effect of a statin on hypertensive nephrosclerosis. We treated stroke-prone spontaneously hypertensive rats (spSHRs) chronically, starting at the age of 4 weeks, with cerivastatin (2 mg/kg per day by gavage) or vehicle. Physiological parameters, plasma chemistry and urine protein excretion were analysed. At 14 weeks of age, the rats had their kidneys removed for use in assays. Compared with vehicle treatment, statin treatment reduced proteinuria and renal injury independently of blood pressure and cholesterol concentrations in spSHRs. Although expression of adhesion molecules and infiltration of inflammatory cells were not different whether or not cerivastatin treatment was used, renal fibrosis was significantly reduced in statin-treated spSHRs. We also found that expression of transforming growth factor-beta1 in kidneys was significantly inhibited in statin-treated spSHRs. Cerivastatin prevents or retards hypertension-induced renal injury via inhibition of renal fibrosis and proteinuria. These results show the potential of statins as protective tools against proteinuric renal diseases, independent of their cholesterol-decreasing effects.Journal of Hypertension 01/2003; 20(12):2465-73. · 4.02 Impact Factor -
Article: HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats.
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ABSTRACT: Recent clinical studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert protective effects against nonhemorrhagic stroke. In a murine cerebral ischemia model produced by occlusion of the middle cerebral artery, statins were shown to reduce infarct size. However, the effect of statins on hypertension-based stroke is unknown. The purpose of this study is to clarify the effect of a statin on stroke in stroke-prone spontaneously hypertensive rats (SHR-SP), in which both cerebral hemorrhage and infarction occur. We treated SHR-SP chronically from 4 weeks of age with cerivastatin (2 mg/kg per day by gavage) or vehicle. The physiological parameters, the incidence of stroke-associated symptoms, and mortality were assessed. At 14 weeks of age, the incidence (13+/-3% versus 37+/-8%; P<0.01) and the size of stroke (1.6+/-0.2 versus 2.2+/-0.1 arbitrary units; P<0.01) were significantly decreased by cerivastatin, although blood pressure and plasma cholesterol levels were not different. Moreover, stroke-associated symptoms and early mortality of SHR-SP were markedly reduced in the statin-treated group (mortality at the age of 15 weeks: 15% versus 50%; P<0.05). Statin treatment significantly reduced superoxide production from nonstroke parenchyma of brain and infiltration of inflammatory cells to the stroke lesions. Our data show that a high dose of statin exerts protection against hypertension-based stroke and ameliorates the disease severity via inhibition of superoxide production and modulation of inflammation in brain.Stroke 01/2003; 34(1):157-63. · 5.73 Impact Factor
