Effects of adenosine A2A receptor agonist, CGS 21680, on blood pressure, cardiac index and arterial conductance in anaesthetized rats.
The effects of 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) on blood pressure, total peripheral resistance, cardiac index, heart rate and arterial conductance in different vascular beds in the presence and absence of hexamethonium (ganglionic blocker) and phenylephrine (alpha 1-adrenoceptor agonist) were investigated in pentobarbitone-anaesthetized rats using a radioactive microsphere technique. CGS 21680 (0.1, 0.3 and 1.0 microgram/kg/min) significantly decreased blood pressure and total peripheral resistance, and increased heart rate and cardiac index. In addition, after infusion with CGS 21680 (0.1, 0.3 and 1.0 microgram/kg/min) arterial conductance in coronary bed significantly increased. However, while CGS 21680 (0.3 and 1.0 microgram/kg/min) significantly increased conductance in skeletal muscle, it significantly decreased splenic arterial conductance. Moreover, CGS 21680 (1.0 microgram/kg/min) significantly increased conductance in cerebral arterial bed. Infusion with hexamethonium (200 micrograms/kg/min) resulted in significant reduction in blood pressure, heart rate and cardiac index whereas stroke volume and total peripheral resistance remained unchanged. In animals that were pretreated with hexamethonium (200 micrograms/kg/min), further administration of CGS 21680 (0.3 microgram/kg/min), compared to CGS 21680 alone, significantly reduced blood pressure, heart rate and cardiac index but did not affect total peripheral resistance or conductance in any vascular bed. Administration of phenylephrine (7 micrograms/kg/min) resulted in a significant increase in blood pressure and total peripheral resistance, and a significant reduction in cardiac index and heart rate. In animals infused with phenylephrine and CGS 21680 combined, in comparison to those animals that received CGS 21680 alone, no significant differences in blood pressure, heart rate, total peripheral resistance, cardiac index or conductance in any vascular beds were found. Our present findings suggest that CGS 21680 decreased blood pressure by decreasing total peripheral resistance, and increased cardiac index possibly through a reflex-mediated increase in heart rate. Moreover the coronary arterial bed is the most sensitive and cerebral arterial bed is the least sensitive to the effects of CGS 21680. In addition, the autonomic nervous system did not appear to play a major role in the actions of CGS 21680 on arterial conductance, and there was no difference in the action of this compound in the states of normal and raised vascular tone.
Nekooeian
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Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Tabrizchi
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R
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003037:Cobalt Radioisotopes; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D008863:Microspheres; D010627:Phenethylamines / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D018048:Receptors, Purinergic P2 / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D014004:Tin Radioisotopes; D014655:Vascular Resistance / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D000959:Antihypertensive Agents; D003037:Cobalt Radioisotopes; D005730:Ganglionic Blockers; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D058910:Purinergic P2 Receptor Agonists; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D014004:Tin Radioisotopes; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D010656:Phenylephrine; D018738:Hexamethonium; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine