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 are 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. Previous research showed that 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 peripheral non-specific antagonist 8-SPT (25 and 50 mg/kg) 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 them. The heart rate increasing effect of CGS 21860 were probably due to a central effect and not simply a baroreceptor reflex response to the blood pressure decrease. To confirm this, we have administered CGS centrally via i.c.v. administration. Preliminary data suggest that CGS increased heart rate with no decrease in blood pressure observed. Thus, adenosine A2a receptors in the central nervous system seem to mediate the heart rate increases observed for CGS.
NIH ExPorter
NIH ExPorter