Effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output and vascular resistance in acute heart failure in the anaesthetized rat.
1. The effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output, blood pressure, mean circulatory filling pressure (Pmcf), arterial and venous resistances, heart rate and left ventricular end-diastolic pressure were assessed in rats with acute heart failure by means of coronary artery occlusion. 2. Animals (n=6 in each group) were divided into five groups: group I, sham-operated vehicle-treated (0.9% saline; 0.018 mL min(-1)); groups II-V, subject to coronary artery occlusion and treated with vehicle (0.9% saline; 0.018 ml min(-1)) and CGS 21680 (0.1, 0.3 and 1.0 microg kg(-1) min(-1)), respectively. Haemodynamic measurements were taken one hour after completion of surgery, ninety minutes after coronary artery occlusion (except in group I), and fifteen minutes after infusion of saline or CGS 21680. 3. Baseline haemodynamic measurements before occlusion were found not to differ significantly between the different groups of animals. However, after occlusion, cardiac output, rate of rise in left ventricular pressure (+ dP/dt) and blood pressure were significantly reduced when compared to corresponding values in sham-operated animals. In addition, occlusion of the coronary artery resulted in a significant elevation in venous resistance, Pmcf and left ventricular end-diastolic pressure as compared to corresponding values in sham-operated animals. 4. Infusion with CGS 21680 at the highest dose significantly reduced blood pressure, arterial resistance and left ventricular end-diastolic pressure when compared to occluded vehicle-treated animals (group II). Administration of CGS 21680 at the highest dose also significantly increased cardiac output (28%) and heart rate (10%) in comparison to occluded vehicle-treated animals. In addition, the highest dose of CGS 21680 significantly reduced Pmcf (9%) and venous resistance (62%) in comparison to occluded vehicle-treated animals. Administration of CGS 21680 did not significantly affect +dP/dt when compared to occluded vehicle-treated animals. 5. The results from the present investigation indicate that occlusion of the coronary artery in rats results in a state of heart failure characterized by reduced arterial pressure and cardiac output, and increased venous resistance, Pmcf and left ventricular end-diastolic pressure. Administration of CGS 21680 to animals with acute heart failure resulted in increased cardiac output which was due to reduced venous resistance, as well as increased heart rate.
Nekooeian
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Department of Pharmacology & Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
Tabrizchi
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D000208:Acute Disease; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects*; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008863:Microspheres; D010627:Phenethylamines / Q000494:pharmacology*; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects*; D016277:Ventricular Function, Left / Q000187:drug effects
D000959:Antihypertensive Agents; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine