Bradykinin and ATP stimulate L-arginine uptake and nitric oxide release in vascular endothelial cells.
The effects of bradykinin and ATP on L-arginine transport and nitric oxide (NO) production were studied in porcine aortic endothelial cells cultured and perfused on microcarriers and deprived of L-arginine for 24 h. Stimulation of cells with bradykinin (100 nM) or ATP (100 microM) resulted in a rapid increase in L-arginine uptake and NO release. In the presence of nitro-L-arginine (100 microM), an inhibitor of NO synthase, the stimulatory effect of bradykinin on L-arginine uptake was partially inhibited while NO release was completely abolished. Nitro-L-arginine alone was not an inhibitor of basal L-arginine transport, suggesting that its inhibitory action was not directly on the L-arginine transporter but a result of the inhibition of NO generation. These data indicate that during agonist-stimulated NO production there is a concomitant increase in the transport of L-arginine into endothelial cells providing a mechanism for the continual generation of NO.
Bogle
R G
RG
Section of Vascular Biology, MRC Clinical Research Centre, Harrow, U.K.
Coade
S B
SB
Moncada
S
S
Pearson
J D
JD
Mann
G E
GE
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D013552:Swine
D019335:Nitroarginine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D001120:Arginine; D006152:Cyclic GMP; D001920:Bradykinin