title: Regression of glomerular and tubulointerstitial injuries by dietary salt reduction with combination therapy of angiotensin II receptor blocker and calcium channel blocker in Dahl salt-sensitive rats.
abstract: A growing body of evidence indicates that renal tissue injuries are reversible. We investigated whether dietary salt reduction with the combination therapy of angiotensin II type 1 receptor blocker (ARB) plus calcium channel blocker (CCB) reverses renal tissue injury in Dahl salt-sensitive (DSS) hypertensive rats. DSS rats were fed a high-salt diet (HS; 4% NaCl) for 4 weeks. Then, DSS rats were given one of the following for 10 weeks: HS diet; normal-salt diet (NS; 0.5% NaCl), NS + an ARB (olmesartan, 10 mg/kg/day), NS + a CCB (azelnidipine, 3 mg/kg/day), NS + olmesartan + azelnidipine or NS + hydralazine (50 mg/kg/day). Four weeks of treatment with HS diet induced hypertension, proteinuria, glomerular sclerosis and hypertrophy, glomerular podocyte injury, and tubulointerstitial fibrosis in DSS rats. A continued HS diet progressed hypertension, proteinuria and renal tissue injury, which was associated with inflammatory cell infiltration and increased proinflammatory cytokine mRNA levels, NADPH oxidase activity and NADPH oxidase-dependent superoxide production in the kidney. In contrast, switching to NS halted the progression of hypertension, renal glomerular and tubular injuries. Dietary salt reduction with ARB or with CCB treatment further reduced blood pressure and partially reversed renal tissues injury. Furthermore, dietary salt reduction with the combination of ARB plus CCB elicited a strong recovery from HS-induced renal tissue injury including the attenuation of inflammation and oxidative stress. These data support the hypothesis that dietary salt reduction with combination therapy of an ARB plus CCB restores glomerular and tubulointerstitial injury in DSS rats.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Kazi
authors.initials: K
authors.lastname: Rafiq
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.affiliation: Division of Nephrology and Hypertension, Osaka City General Hospital, Osaka, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Konishi
authors.affiliation: Division of Nephrology and Hypertension, Osaka City General Hospital, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Division of Nephrology and Hypertension, Osaka City General Hospital, Osaka, Japan.
authors.forename: Chizuko
authors.initials: C
authors.lastname: Kitabayashi
authors.affiliation: Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Mori
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.affiliation: Division of Nephrology and Hypertension, Osaka City General Hospital, Osaka, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Imanishi
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004039:Diet, Sodium-Restricted; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression; D005786:Gene Expression Regulation; D006973:Hypertension / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D020303:Rats, Inbred Dahl; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D051437:Renal Insufficiency / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D057911:Angiotensin Receptor Antagonists; D002121:Calcium Channel Blockers; D016207:Cytokines; D004095:Dihydropyridines; D007093:Imidazoles; D018161:Receptors, Mineralocorticoid; D013777:Tetrazoles; D001383:Azetidinecarboxylic Acid; C437965:olmesartan; D019255:NADPH Oxidases; C061679:azelnidipine