Effects of the AT1 receptor blocker losartan and the calcium channel blocker benidipine on the accumulation of lipids in the ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-03

AUTHORS

Nobukazu Ishizaka, Makiko Hongo, Matsuzaki, Kyoko Furuta, Kan Saito, Ryota Sakurai, Aiko Sakamoto, Kazuhiko Koike, Ryozo Nagai

ABSTRACT

Unfavorable lipid accumulation may occur in the kidneys in the presence of metabolic syndrome and diabetes. The aim of this study was to investigate whether excess lipids would accumulate in the kidneys of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of metabolic syndrome. From 34 weeks of age, OLETF rats were treated orally with a calcium channel blocker, benidipine (3 mg kg(-1) per day), or an AT1 receptor blocker, losartan (25 mg kg(-1) per day), for 8 weeks. Blood pressure was slightly but significantly higher in the untreated OLETF rats (149+/-4 mm Hg) than in Long-Evans Tokushima Otsuka (LETO) rats (136+/-2 mm Hg), and both losartan (135+/-3 mm Hg) and benidipine (138+/-3 mm Hg) reduced blood pressure in OLETF rats to a level comparable to that in LETO rats. Tissue content of triglycerides (TG) was greater in OLETF rats than in LETO rats (6.24+/-3.77 and 2.85+/-1.32 microg mg(-1) x tissue, respectively), and both losartan and benidipine reduced these values. Histological analysis showed lipid droplets in tubular cells in which increased dihydroethidium fluorescence was present. Expression of peroxisome proliferator-activated receptor-alpha, PGC-1alpha and uncoupling protein-2 was found to be higher in OLETF rats than in LETO rats; however, the expression of these genes was not altered by treatment with either antihypertensive drug. In contrast, both losartan and benidipine increased the amount of total and phosphorylated forms of AMP kinase and the expression of carnitine palmitoyltransferase-1 (CPT-1). In conclusion, treatment of OLETF rats with losartan and benidipine reduced the tissue content of TG, decreased the production of superoxide and regulated the expression of genes related to fatty acid oxidation such as AMP-activated protein kinase and CPT-1 in the kidneys. More... »

PAGES

263

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/hr.2009.224

DOI

http://dx.doi.org/10.1038/hr.2009.224

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1024510731

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20057486


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298 https://www.grid.ac/institutes/grid.26999.3d schema:alternateName University of Tokyo
299 schema:name Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan
300 Department of Gastroenterology, University of Tokyo Graduate School of Medicine, Tokyo, Japan
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