Expression of intrahepatic inducible nitric oxide synthetase mRNA correlates with production of nitric oxide during intraportal isogeneic and allogeneic rat islet transplantation.
Intrahepatic NO production is related to the islet mass transplanted. Nitric oxide production is higher in recipients of allogeneic rather than syngeneic islets. In addition, in allogeneic recipients a possible second peak of NO production was observed at 120 hours corresponding to the time of cellular rejection of the islet grafts (P = .22 vs 96 hours). Finally, the time to rejection of Wistar rat donor islets transplanted into Lewis rat diabetic recipients treated with NMA was not affected. However, inhibiting NO production in the minimal islet transplant model decreased the time to islet function, it does not affect the time to clinical rejection in recipients of a high number of allogeneic islet, which functions immediately. High-level NO has been shown to inhibit T-cell activation in vitro, and thus decreasing the levels by administrating NMA may accentuate the rejection response, canceling out the beneficial effect that might otherwise have occurred on islet function. Further experiments are required to clarify these issues.
Stevens
R B
RB
Department of Surgery, University of Minnesota, Minneapolis.
Ansite
J D
JD
Lokeh
A
A
Rossini
T J
TJ
Mills
C D
CD
Sutherland
D E
DE
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000628:therapy*; D004790:Enzyme Induction; D015870:Gene Expression; D006084:Graft Rejection / Q000503:physiopathology; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D016133:Polymerase Chain Reaction; D011168:Portal System; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous / Q000502:physiology; D014185:Transplantation, Isogeneic / Q000502:physiology; D019323:omega-N-Methylarginine
D009566:Nitrates; D012333:RNA, Messenger; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases