Cardiovascular pharmacology of the A2A adenosine receptor antagonist, SCH 58261, in the rat.

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 A2A 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 A2A 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 A2A selective receptor antagonist properties in vivo. Its effect on cardiovascular sympathetic outflow further suggests that endogenous adenosine exerts a tonic vascular regulation through A2A receptors. Therefore, SCH 58261 can be a useful pharmacological tool for clarifying A2A-mediated cardiovascular actions of adenosine.

• Authors: A Monopoli, C Casati, G Lozza, A Forlani, E Ongini
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 285 Issue 1 Pg. 9-15 (Apr 1998) ISSN: 0022-3565 [Print] United States
• PMID: 9535988 (Publication Type: Journal Article)

Chemical References

• 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
• Adrenergic Antagonists
• Purinergic P1 Receptor Antagonists
• Pyrimidines
• Triazoles
• Propranolol
• Phentolamine

Topics

• Adrenergic Antagonists (pharmacology)
• Animals
• Blood Pressure (drug effects)
• Drug Interactions
• Heart Rate (drug effects)
• Hemodynamics (drug effects)
• Male
• Phentolamine (pharmacology)
• Propranolol (pharmacology)
• Purinergic P1 Receptor Antagonists
• Pyrimidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Triazoles (pharmacology)