Hemodynamic responses to intravenous (i.v.) injection of
DPMA [N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]
adenosine); PD 125,944], a potent
adenosine agonist with a 32-fold selectivity for the
adenosine-2 (A2) receptor subtype, were characterized in conscious and anesthetized rats. In conscious rats instrumented with miniaturized pulsed-Doppler flow probes, i.v. injection of increasing doses of
DPMA (3-30 micrograms/kg) had little effect on mean arterial pressure (MAP, maximal decrease -8 +/- 4 mm Hg) or renal and mesenteric resistance (maximal change 8 +/- 14 and 0 +/- 15%, respectively). In contrast,
DPMA markedly reduced MAP (maximal decrease -61 +/- 8 mm Hg) in a dose-dependent (1-30 micrograms/kg) fashion in
pentobarbital-anesthetized rats. The A2 agonist also caused a sustained, dose-dependent increase in heart rate (HR, maximal increase 75 +/- 12 beats/min) in conscious rats. The
tachycardia and decrease in arterial pressure were completely reversed by i.v. administration of
CGS 15943 (250 micrograms/kg), a selective
adenosine receptor antagonist. Pretreatment with
propranolol or
hexamethonium significantly reduced but did not abolish the
tachycardia, suggesting that the increase in HR was mediated only partially through reflex increases in sympathetic tone. These data indicate that (a)
anesthesia potentiates the depressor actions of
DPMA and (b) stimulation of A2 receptors increases HR through both direct and indirect mechanisms of action.