title: A high-salt diet enhances leukocyte adhesion in association with kidney injury in young Dahl salt-sensitive rats.
abstract: Salt-sensitive hypertension is associated with severe organ damage. Generating oxygen radicals is an integral component of salt-induced kidney damage, and activated leukocytes are important in oxygen radical biosynthesis. We hypothesized that a high-salt diet causes the upregulation of immune-related mechanisms, thereby contributing to the susceptibility of Dahl salt-sensitive rats to hypertensive kidney damage. For verifying the hypothesis, we investigated leukocytes adhering to retinal vessels when Dahl salt-sensitive rats were challenged with a high-salt (8% NaCl) diet using acridine orange fluoroscopy and a scanning laser ophthalmoscope. The high-salt diet increased leukocyte adhesion after 3 days and was associated with a significant increase in mRNA biosynthesis of monocyte chemotactic protein-1 and intercellular adhesion molecule-1 (ICAM-1) -related molecules in the kidney. Losartan treatment did not affect increased leukocyte adhesion during the early, pre-hypertensive phase of high salt loading; however, losartan attenuated the adhesion of leukocytes during the hypertensive stage. Moreover, the inhibition of leukocyte adhesion in the pre-hypertensive stage by anti-CD18 antibodies decreased tethering of leukocytes and was associated with the attenuation of functional and morphological kidney damage without affecting blood pressure elevation. In conclusion, a high-salt challenge rapidly increased leukocyte adhesion through the over-expression of ICAM-1. Increased leukocyte adhesion in the pre-hypertensive stage is responsible for subsequent kidney damage in Dahl salt-sensitive rats. Immune system involvement may be a key component that initiates kidney damage in a genetic model of salt-induced hypertension.
authors.affiliation: Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.|Department of Ophthalmology, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Department of Cardiology, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Division of Clinical Nutrition, Faculty of Home Economics, Kyoritsu Women's University, Tokyo, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Kawabata
authors.affiliation: Department of Medicine, Moka Hospital, Moka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Numabe
authors.affiliation: Medical Retina, Singapore National Eye Centre, Singapore, Singapore.|Medical Retina, Singapore Eye Research Institute, Singapore, Singapore.|The Ophthalmology & Visual Sciences Academic Clinical Program, Duke-NUS Medical School, National University of Singapore, Singapore, Singapore.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yanagi
authors.affiliation: Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
authors.affiliation: Division of Clinical Nutrition, Faculty of Home Economics, Kyoritsu Women's University, Tokyo, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Uehara
authors.affiliation: Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Araie
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D018932:Chemokine CCL2 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D012982:Sodium, Dietary / Q000494:pharmacology*
chemical_list: D018932:Chemokine CCL2; D012982:Sodium, Dietary; D018799:Intercellular Adhesion Molecule-1