Hyperammonemia inhibits platelet aggregation in rats.
The effect of hyperammonemia on ex vivo platelet function and in vivo nitric oxide synthesis was evaluated in rats. In addition, mitochondrial energy production was assessed from the fluorescence intensity of tetramethylrhodamine ethyl ester (TMRE). Continuous ammonium acetate infusion significantly reduced ex vivo platelet aggregation concomitant with a decrease of the platelet cytoplasmic ATP level. The serum level of L-arginine, as well as the levels of nitrite and nitrate (oxidative by-products of nitric oxide), increased with ammonium infusion. Prior administration of N omega-nitro-L-arginine methyl ester, a competitive inhibitor of nitric oxide synthase, did not affect the ammonia-induced rise in L-arginine, but substantially attenuated the associated decrease of platelet ATP and TMRE fluorescence as well as diminishing the anti-aggregatory effect of ammonia infusion. These findings suggest that the synthesis of nitric oxide from L-arginine is accelerated by continuous ammonium infusion and inhibits ex vivo platelet aggregation in the rat, probably by reducing mitochondrial energy production.
Shinya
H
H
Department of Emergency & Critical Care Medicine, Kansai Medical University, Osaka, Japan.
Matsuo
N
N
Takeyama
N
N
Tanaka
T
T
D000085:Acetates / Q000008:administration & dosage*; D000255:Adenosine Triphosphate / Q000097:blood*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D010974:Platelet Aggregation / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D012235:Rhodamines
D000085:Acetates; D004791:Enzyme Inhibitors; D000644:Quaternary Ammonium Compounds; D012235:Rhodamines; D009569:Nitric Oxide; C005358:tetramethylrhodamine; D000255:Adenosine Triphosphate; C018824:ammonium acetate; D019331:NG-Nitroarginine Methyl Ester