Tetrahydrobiopterin-dependent formation of endothelium-derived relaxing factor (nitric oxide) in aortic endothelial cells.
Inhibition of tetrahydrobiopterin (H4biopterin) biosynthesis in endothelial cells almost completely abolished the agonist-induced formation of endothelium-derived relaxing factor (EDRF) (NO). This inhibitory effect could be antagonized when H4biopterin biosynthesis was restored by activating a salvage pathway. These data indicate that the formation of EDRF strictly depends on the presence of intracellular H4biopterin, which, in addition to Ca2+, may represent a further physiological and/or pathophysiological regulatory of endothelial NO synthases.
Schmidt
K
K
Institut für Pharmakodynamik und Toxikologie, Universität Graz, Austria.
Werner
E R
ER
Mayer
B
B
Wachter
H
H
Kukovetz
W R
WR
D000818:Animals; D001011:Aorta; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D007042:Hypoxanthines / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D013552:Swine
D007042:Hypoxanthines; D001708:Biopterins; D009569:Nitric Oxide; C017202:2,4-diaminohypoxanthine; C003402:sapropterin