In the present study, we investigated the cardiovascular effects of intravenously injected
uridine or
cytidine, and the role of
adenosine receptors in mediating these effects, in conscious normotensive rats. Intravenous (i.v.) administration of
uridine (124, 250, 500 mg/kg) dose-dependently decreased arterial pressure and heart rate.
Cytidine (124, 250, 500 mg/kg; i.v.) produced slight dose-related
hypotension without changing heart rate. Plasma
uridine and
cytidine concentrations increased time- and dose-dependently while plasma
adenosine levels did not change after injection of the respective
nucleosides. Pretreatment with intravenous
caffeine (20 mg/kg),
8-phenyltheophylline (8-PT) (1 mg/kg), nonselective
adenosine receptor antagonists, or 8-p-sulfophenyltheophylline (8-SPT) (20 mg/kg), a nonselective
adenosine receptor antagonist which does not cross the blood-brain barrier, abolished the cardiovascular effects of
uridine (250 mg/kg; i.v.) or
cytidine (250 mg/kg; i.v.). Intracerebroventricular (i.c.v.)
caffeine (200 microg) or 8-SPT (50 microg) pretreatment did not change the magnitude of the cardiovascular responses induced by
nucleosides. Intravenous 8-cyclopenthyl-1,3-dipropylxanthine (
DPCPX) (5 mg/kg), a selective
adenosine A(1) receptor antagonist, greatly attenuated the cardiovascular responses to
uridine and
cytidine. Pretreatment with 3,7,-dimethyl-1-propargylxanthine (
DMPX) (2 mg/kg), an
adenosine A(1)/A(2) receptor antagonist, attenuated
hypotension induced by
uridine and blocked the arterial pressure decrease in response to
cytidine.
Uridine-induced
bradycardia was blocked by
DMPX. 4-(2-[7-amino-2-(2-furyl[1,2,4]-triazolo[2,3-a[1,3,5]triazin-5-yl-aminoethyl)
phenol (
ZM241385) (1 mg/kg; i.v.), a selective
adenosine A(2A) receptor antagonist, pretreatment produced an only very small blockade in the first minute of the hypotensive effects of
uridine without affecting the
bradycardia.
ZM241385 pretreatment completely blocked
cytidine's hypotensive effect. In Langendorff-perfused rat heart preparation,
uridine (10(-3) M), but not
cytidine, decreased the heart rate. Our results show that intravenously injected
uridine or
cytidine is able to decrease arterial pressure by activating peripheral
adenosine receptors. The data also implicates that the mainly
adenosine A(1) receptor activation is involved in the
uridine-induced cardiovascular effects, while both
adenosine A(1) and A(2A) receptor activations mediate the
cytidine's effects.