Nitric oxide synthase activity in renal ischemia-reperfusion injury in the rat: implications for renal transplantation.
Cadaveric kidney transplants with delayed graft function have poorer graft survival by an unknown mechanism. Nitric oxide, produced by nitric oxide synthase (NOS), has a proven role in both recovery of ischemia and promotion of rejection. We therefore wished to study the patterns of NOS activity in a model of renal ischemia. The left renal pedicle of Fisher rats was occluded for 1 hr. Both kidneys were removed at various times and frozen. Renal NOS activity was measured by conversion of [3H]arginine to [3H]citrulline and the content of endothelial NOS isoenzyme (eNOS) was compared by Western blot. NOS activity increased significantly in the left ischemic kidney over the first 24 hr, from a control of 33.8 pmol/min/mg to 79.8 at 2 hr and 56.8 at 24 hr. NOS activity then dropped below baseline, returning to near normal levels at day 21. eNOS content was stimulated over the entire time course, consistent with the presence of an eNOS inhibitor. Oral treatment with the NOS substrate L-arginine at 5 g/L significantly hastened the return of serum creatinine to baseline, if simultaneous contralateral nephrectomy was performed. The lazaroid U74389G given perioperatively also improved renal function and hastened recovery of NOS activity. Because nitric oxide plays an important role in maintaining blood flow during recovery from renal ischemia, the observed decrease in NOS activity may be prevented by perioperative treatment with oral L-arginine and corticosteroids. In addition, U74389G may provide a clinically useful method of minimizing and/or shortening DGF, thereby improving graft function and survival.
Shoskes
D A
DA
Department of Surgery, Harbor-UCLA Medical Center, UCLA School of Medicine, Torrance, California 90509, USA.
Xie
Y
Y
Gonzalez-Cadavid
N F
NF
D000818:Animals; D007511:Ischemia / Q000201:enzymology*; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011281:Pregnatrienes / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000201:enzymology*
D011281:Pregnatrienes; C074965:U 74389F; D019001:Nitric Oxide Synthase