Abstract

We characterized the in vivo cardiovascular profile of SCH 58261, 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine, a selective A_2A adenosine receptor antagonist, in conscious, freely moving rats by use of the telemetry system. In normotensive rats, SCH 58261, at 10 mg/kg i.p., significantly (P < .05) inhibited hypotension and tachycardia induced by the A_2A receptor agonist 2-hexynyl-5′-N-ethylcarboxamidoadenosine (0.01 mg/kg i.p.), but not the bradycardic effect caused by the A₁ receptor agonist 2-chloro-N⁶-cyclopentyladenosine (0.03 mg/kg i.p.). SCH 58261, when administered alone, at 0.1 and 1 mg/kg i.p., did not induce significant hemodynamic changes, but at 10 mg/kg i.p., it slightly increased both systolic blood pressure (SBP) and diastolic blood pressure (DBP) (+19 ± 3 and +16 ± 2 mm Hg, respectively; P < .01) and heart rate (HR) (+85 ± 5 beats/min; P < .01). These effects were inhibited by adrenergic blockade with propranolol (30 mg/kg i.p.) and phentolamine (10 mg/kg i.p.): −5 ± 3 mm Hg on DBP and −12 ± 11 beats/min on HR (P < .01). In spontaneously hypertensive rats, SCH 58261, at 3 and 10 mg/kg i.p., increased weakly both SBP (+19 ± 5 mm Hg and +25 ± 4 mm Hg) and DBP (+14 ± 4 mm Hg and +23 ± 4 mm Hg)vs. vehicle (P < .01) and HR (+45 ± 17 and +64 ± 18 beats/min vs. vehicle, respectively; P < .01). The data indicate that SCH 58261 retains A_2A selective receptor antagonist properties in vivo. Its effect on cardiovascular sympathetic outflow further suggests that endogenous adenosine exerts a tonic vascular regulation through A_2A receptors. Therefore, SCH 58261 can be a useful pharmacological tool for clarifying A_2A-mediated cardiovascular actions of adenosine.