Scavenging of nitric oxide by an antagonist of adenosine receptors.
Chronic treatment of rats with 1,3-dipropyl-8-sulfophenylxanthine (DPSPX), an antagonist of adenosine receptors, causes hypertension, cardiovascular hypertrophy and hyperplasia and impaired endothelium-dependent vasodilatation. An accelerated degradation of nitric oxide (NO) by scavenging molecules could account for endothelial dysfunction and trophic changes in this hypertension. Our aim was to determine whether DPSPX is a scavenger of NO and if this putative effect is shared by caffeine (1,3,7-trimethylxanthine) and DPCPX (1,3-dipropyl-8-ciclopentylxanthine), which are also adenosine receptor antagonists but do not induce hypertension in rats. This effect was evaluated by electrochemical and spectrofluorometric assays. Urinary NOx (nitrate + nitrite) excretion was also evaluated in controls and DPSPX-treated rats as a marker for NO bioavailability. DPSPX behaved as a scavenger of NO in a concentration-dependent manner in the electrochemical and spectrofluorometric assays. Caffeine and DPCPX had no scavenging effect. DPSPX-treated rats had decreased excretion of urinary nitrites. We can conclude that: DPSPX has NO scavenging properties that may be involved in the alterations described for DPSPX-hypertensive rats; this NO-scavenging effect is not shared by caffeine and DPCPX, which are also xanthine derivatives and adenosine antagonists.
Sousa
Teresa
T
Institute of Pharmacology and Therapeutics, Faculty of Medicine of Porto, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal.
Fernandes
Eduarda
E
Nunes
Carla
C
Laranjinha
João
J
Carvalho
Félix
F
Pinho
Dora
D
Morato
Manuela
M
Albino-Teixeira
António
A
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008297:Male; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000008:administration & dosage*; D014970:Xanthines / Q000494:pharmacology*
D058917:Adenosine A2 Receptor Antagonists; D016166:Free Radical Scavengers; D009566:Nitrates; D009573:Nitrites; D043682:Receptor, Adenosine A1; D014970:Xanthines; D009569:Nitric Oxide; D002110:Caffeine; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine