Long-Term Administration of Rho-Kinase Inhibitor Ameliorates Renal Damage in Malignant Hypertensive Rats
-
- Yayoi Ishikawa
- From the Department of Hypertension and Cardiorenal Medicine (Y.I., T.N., K.I., H.O., H.M.) and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
-
- Toshio Nishikimi
- From the Department of Hypertension and Cardiorenal Medicine (Y.I., T.N., K.I., H.O., H.M.) and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
-
- Kazumi Akimoto
- From the Department of Hypertension and Cardiorenal Medicine (Y.I., T.N., K.I., H.O., H.M.) and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
-
- Kimihiko Ishimura
- From the Department of Hypertension and Cardiorenal Medicine (Y.I., T.N., K.I., H.O., H.M.) and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
-
- Hidehiko Ono
- From the Department of Hypertension and Cardiorenal Medicine (Y.I., T.N., K.I., H.O., H.M.) and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
-
- Hiroaki Matsuoka
- From the Department of Hypertension and Cardiorenal Medicine (Y.I., T.N., K.I., H.O., H.M.) and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
抄録
<jats:p>We have shown recently that fasudil, a Rho-kinase inhibitor, has renoprotective effects in salt-sensitive hypertensive rats. We hypothesized that activation of Rho-kinase is involved in the pathogenesis of glomerulosclerosis in malignant hypertensive rats. To test this hypothesis, we studied the following 4 groups: control Wistar–Kyoto rats, untreated deoxycorticosterone-acetate salt spontaneously hypertensive rats (DOCA-SHR), low-dose fasudil-treated DOCA-SHR, and high-dose fasudil-treated DOCA-SHR. After 3 weeks of treatment, the effects of fasudil were examined. DOCA-SHR was characterized by increased blood pressure (BP); increased kidney weight; decreased renal function; increased proteinuria; abnormal histological findings; increased monocyte/macrophage infiltration; increased urinary 8-isoprostran levels; increased gene expression of collagen I, collagen III, transforming growth factor-β, and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits (p40phox, p47phox, and p67phox); and decreased gene expression of endothelial NO synthase (eNOS) in the renal cortex as compared with Wistar–Kyoto rats. Long-term high-dose fasudil treatment significantly improved renal function and histological findings without changing BP, as compared with untreated DOCA-SHR. Interestingly, long-term fasudil treatment significantly decreased monocyte/macrophage infiltration and urinary 8-isoprostran excretion, in association with decreased mRNA levels of transforming growth factor-β, collagen I, collagen III, and NADPH oxidase subunits (p40phox, p47phox, and p67phox), and increased mRNA levels of eNOS in the renal cortex. Long-term low-dose fasudil treatment tended to improve these variables slightly but did not affect most of them significantly. Our results suggest that long-term fasudil treatment provides renoprotective effects independent of BP-lowering activity. These renoprotective effects are associated with inhibition of extracellular matrix gene expression, monocyte/macrophage infiltration, oxidative stress, and upregulation of eNOS gene expression.</jats:p>
収録刊行物
-
- Hypertension
-
Hypertension 47 (6), 1075-1083, 2006-06
Ovid Technologies (Wolters Kluwer Health)
- Tweet
キーワード
詳細情報
-
- CRID
- 1362544419729546368
-
- NII論文ID
- 30022678696
-
- ISSN
- 15244563
- 0194911X
-
- データソース種別
-
- Crossref
- CiNii Articles
- KAKEN