Recent research has focused on the role that adenosine receptor subtypes in cardiovascular function. Adenosine plays a role in the behavioral effects of caffeine, one of the most widely used drugs in the world. Rats have been implanted with telemetry devices for recording blood pressure and heart rate. Various adenosine agonists and antagonists were then administered i.p. and blood pressure and heart rate were recorded for 1 hour. The adenosine A1 agonist CPA in doses up to 0.3 mg/kg produced large decreases in both blood pressure and heart rate. The adenosine A2a agonist CGS 21680 in doses up to 0.5 mg/kg did not have as large an effect on blood pressure, but dramatically increased heart rate. The effects of CGS 21680 were antagonized by the A2a antagonist MSX-3 (3.0 mg/kg), while the effects of CPA were not. However, the adenosine antagonist CPT (4.8 mg/kg) blocked the effects of CPA and had little effect on CGS 21680. Neither antagonist on its own affected either blood pressure or heart rate. Caffeine (30 mg/kg) slightly increased both blood pressure and heart rate. When given as a pretreatment caffeine blocked the effects of CPA, but only partially reversed the effects of CGS 21860. The peripheral non-specific antagonist 8-SPT (25 mg/kg) had effects similar to caffeine. In particular, 8-SPT blocked the effects of CPA and appeared to reverse the blood pressure decreases following CGS, but had no effect on the heart rate increases. These results suggest that adenosine has potent effects on cardiovascular function. The effects of CPA appeared to be mediated by peripheral receptors as 8-SPT could block the effects. The heart rate increasing effect of CGS 21860 is probably due to a central effect and is not simply a baroreceptor reflex response to the blood pressure decrease. Caffeine functions primarily as an adenosine A1 antagonist, although some A2a action cannot be ruled out.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000009-17
Application #
6680308
Study Section
(BNRB)
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2002
Total Cost
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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