Tetrahydrobiopterin synthesis inhibitors induce nitric oxide synthesis in rat aorta.
1. Incubation of rato aortic rings with tetrahydrobiopterin synthesis inhibitors (NAS or DAHP) significantly decreased contractions to phenylephrine. These two compounds significantly potentiated the vascular hyporeactivity induced by endotoxin. Inhibitors of nitric oxide synthesis (NLA or MLA) restored the contractile responses to this alpha 1-agonist in NAS- or DAHP-treated control rings and abolished the NAS- or DAHP-induced increased hyporeactivity to PE in endotoxin-treated aortic rings. These observations suggest that treatment of isolated blood vessels with BH4 synthesis inhibitors induces the production of NO.synthesis, resulting in turn in a vascular hyporeactivity to PE potentiated in endotoxin-treated preparations.
Joly
G A
GA
Department of Genitourinary Oncology, University of Texas M. D. Anderson Cancer Center, Houston, USA.
Kilbourn
R G
RG
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006136:GTP Cyclohydrolase / Q000037:antagonists & inhibitors*; D007042:Hypoxanthines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000096:biosynthesis*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014661:Vasoconstriction
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D007042:Hypoxanthines; D008070:Lipopolysaccharides; D010656:Phenylephrine; D009569:Nitric Oxide; D012701:Serotonin; D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase; D006136:GTP Cyclohydrolase; C017202:2,4-diaminohypoxanthine; C006389:N-acetylserotonin