PMID- 18313046
OWN - NLM
STAT- MEDLINE
DCOM- 20080710
LR  - 20161124
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 584
IP  - 1
DP  - 2008 Apr 14
TI  - Hypotensive effects of intravenously administered uridine and cytidine in 
      conscious rats: involvement of adenosine receptors.
PG  - 125-36
LID - 10.1016/j.ejphar.2008.01.044 [doi]
AB  - 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.
FAU - Yilmaz, M Sertac
AU  - Yilmaz MS
AD  - Uludag University Faculty of Medicine, Department of Pharmacology and Clinical 
      Pharmacology, 16059, Gorukle, Bursa, Turkey.
FAU - Coskun, Cenk
AU  - Coskun C
FAU - Suzer, Oner
AU  - Suzer O
FAU - Yalcin, Murat
AU  - Yalcin M
FAU - Mutlu, Duygu
AU  - Mutlu D
FAU - Savci, Vahide
AU  - Savci V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080209
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Adenosine A1 Receptor Agonists)
RN  - 0 (Adenosine A2 Receptor Agonists)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Receptor, Adenosine A1)
RN  - 0 (Receptor, Adenosine A2A)
RN  - 0 (Triazines)
RN  - 0 (Triazoles)
RN  - 0 (Xanthines)
RN  - 0 (ZM 241385)
RN  - 3G6A5W338E (Caffeine)
RN  - 5CSZ8459RP (Cytidine)
RN  - 5YFR5SPS6T (3,7-dimethyl-1-propargylxanthine)
RN  - 80206-91-3 (8-(4-sulfophenyl)theophylline)
RN  - 9PTP4FOI9E (1,3-dipropyl-8-cyclopentylxanthine)
RN  - C137DTR5RG (Theophylline)
RN  - K72T3FS567 (Adenosine)
RN  - OBD445WZ5P (Theobromine)
RN  - WHI7HQ7H85 (Uridine)
SB  - IM
MH  - Adenosine/blood
MH  - *Adenosine A1 Receptor Agonists
MH  - *Adenosine A2 Receptor Agonists
MH  - Animals
MH  - Antihypertensive Agents/*administration & dosage/adverse effects/blood
MH  - Blood Pressure/*drug effects
MH  - Caffeine/administration & dosage
MH  - Carotid Arteries/*drug effects/metabolism/physiopathology
MH  - Consciousness
MH  - Cytidine/*administration & dosage/adverse effects/blood
MH  - Dose-Response Relationship, Drug
MH  - Heart Rate/drug effects
MH  - Hypotension/*chemically induced/metabolism/physiopathology
MH  - Injections, Intravenous
MH  - Injections, Intraventricular
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Adenosine A1/metabolism
MH  - Receptor, Adenosine A2A/metabolism
MH  - Theobromine/administration & dosage/analogs & derivatives
MH  - Theophylline/administration & dosage/analogs & derivatives
MH  - Time Factors
MH  - Triazines/administration & dosage
MH  - Triazoles/administration & dosage
MH  - Uridine/*administration & dosage/adverse effects/blood
MH  - Ventricular Function, Left/drug effects
MH  - Ventricular Pressure/drug effects
MH  - Xanthines/administration & dosage
EDAT- 2008/03/04 09:00
MHDA- 2008/07/11 09:00
CRDT- 2008/03/04 09:00
PHST- 2007/08/22 00:00 [received]
PHST- 2007/12/27 00:00 [revised]
PHST- 2008/01/22 00:00 [accepted]
PHST- 2008/03/04 09:00 [pubmed]
PHST- 2008/07/11 09:00 [medline]
PHST- 2008/03/04 09:00 [entrez]
AID - S0014-2999(08)00130-1 [pii]
AID - 10.1016/j.ejphar.2008.01.044 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2008 Apr 14;584(1):125-36. doi: 10.1016/j.ejphar.2008.01.044. 
      Epub 2008 Feb 9.