Role of central and peripheral adenosine receptors in the cardiovascular responses to intraperitoneal injections of adenosine A_1 and A_(2A) subtype receptor agonists

摘要

1. The cardiovascular effects of the adenosine A_1 receptor agonist N~6-cyclopentyladenosine (CPA) and the adenosine A_(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamido-adenosine (CGS 21680) were investigated in rats implanted with telemetry transmitters for the measurement of blood pressure and heart rate. 2. Intraperitoneal (i.p.) injections of the adenosine A_1 receptor agonist CPA led to dose-dependent decreases in both blood pressure and heart rate. These effects of 0.3 mg kg~(-1) CPA were antagonized by i.p. injections of the adenosine A_1 receptor antagonist 8-cyclopentyl-1,3-dimethyl-xanthine (CPT), but not by i.p. injections of the adenosine A_(2A) receptor antagonist 3-(3-hydroxypropyl)-8-(m-methoxystyryl)-7-methyl-1-propargylxanthine phosphate disodium salt (MSX-3). Injections (i.p.) of the peripherally acting nonselective adenosine antagonist 8-sulfophenyltheophylline (8-SPT) and the purported nonselective adenosine antagonist caffeine also antagonized the cardiovascular effects of CPA. 3. The adenosine A_(2A) agonist CGS 21680 given i.p. produced a dose-dependent decrease in blood pressure and an increase in heart rate. These effects of 0.5mg kg~(-1) CGS 21680 were antagonized by i.p. injections of the adenosine A_(2A) receptor antagonist MSX-3, but not by i.p. injections of the antagonists CPT, 8-SPT or caffeine. 4. Central administration (intracerebral ventricular) of CGS 21680 produced an increase in heart rate, but no change in blood pressure. MSX-3 given i.p. antagonized the effects of the central injection of CGS 21680. 5. These results suggest that adenosine A_1 receptor agonists produce decreases in blood pressure and heart rate that are mediated by A_1 receptors in the periphery, with little or no contribution of central adenosine A_1 receptors to those effects. 6. The heart rate increasing effect of adenosine A_(2A) agonists appears to be mediated by adenosine A_(2A) receptors in the central nervous system. The blood pressure decreasing effect of adenosine A_(2A) agonists is most probably mediated in the periphery.