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Induction of LOX‐1 and iNOS expressions by ischemia‐reperfusion of rat kidney and the opposing effect of L‐arginine
Author(s) -
Kosaka Hiroaki,
Yoneyama Hirohito,
Zhang Ling,
Fujii Shigemoto,
Yamamoto Akira,
Igarashi Junsuke
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0585com
Subject(s) - nitric oxide , arginine , nitric oxide synthase , kidney , ischemia , endothelial nos , reperfusion injury , endocrinology , transplantation , medicine , chemistry , pharmacology , biochemistry , enos , amino acid
Lectin‐like oxidized low‐density lipoprotein receptor (LOX‐1) is a newly identified endothelial cell surface major receptor for oxidatively modified low‐density lipoprotein. Progression of arthrosclerosis in the donor organ after organ transplantation is a major problem. We hypothesized that ischemia‐reper‐fusion induces LOX‐1. After 1 h ischemia of bilateral kidneys plus 3, 6, or 12 h reperfusion, we first revealed that LOX‐1 mRNA expression was increased in renal cortex and medulla at 6 h after reperfusion, which was decreased by l ‐arginine supplement. Plasma nitric oxide (NO) end‐product nitrite plus nitrate and inducible nitric oxide synthase (NOS) expression were increased after reperfusion of 6 h. However, NOS substrate l ‐arginine did not augment but markedly decreased plasma NO end product, because l ‐arginine supplement suppressed inducible NOS expression in kidney. We hypothesized that available l ‐arginine is depleted by ischemia‐reperfusion, leading to inducible NOS induction. Ischemia decreased l ‐arginine levels in kidney and l ‐arginine supplement increased NO end products in renal cortex in the earliest phase of reperfusion. These results disclosed for the first time that a deficiency in l ‐arginine by ischemia reperfusion causes uncoupling of constitutive NOS, which induces inducible NOS and LOX‐1, implying why l ‐arginine is effective for stroke or transplantation in preventing atherosclerotic progress.—Kosaka, H., Yoneyama, H., Zhang, L., Fujii, S., Yamamoto, A., Igarashi, J. Induction of LOX‐1 and iNOS expressions by ischemia‐reperfusion of rat kidney and the opposing effect of L‐arginine. FASEB J. 17, 636–643 (2003)