Induction of LOX-1 and iNOS expressions by ischemia-reperfusion of rat kidney and the opposing effect of L-arginine.
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-reperfusion 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
Hiroaki
H
The 2nd Department of Physiology, Kagawa Medical University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. hkosaka@kms.ac.jp
Yoneyama
Hirohito
H
Zhang
Ling
L
Fujii
Shigemoto
S
Yamamoto
Akira
A
Igarashi
Junsuke
J
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000097:blood / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000235:genetics*; D051131:Receptors, Oxidized LDL; D015427:Reperfusion Injury / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors
D009566:Nitrates; D009573:Nitrites; C495136:OLR1 protein, rat; D012333:RNA, Messenger; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D001708:Biopterins; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase; C003402:sapropterin