The role of adenosine in rat coronary flow regulation during respiratory and metabolic acidosis.
The role of adenosine in rat coronary flow regulation during acidosis was evaluated in isolated, perfused, Langendorff rat heart preparations exposed to brief periods of hypercapnic or metabolic acidosis. Acidosis resulted in increases in coronary flow rate, in conjunction with decreases in ventricular contractile tensions. Heart rates were non-significantly increased. Two non-selective adenosine antagonists, caffeine and 8-phenyltheophylline, markedly attenuated the increases in coronary flow during hypercapnic acidosis without affecting the decline in contractile tension or the heart rate. ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a]triazin-5-ylami no]ethyl)phenol), a selective adenosine A2A receptor antagonist, also blocked hypercapnic acidosis-evoked coronary flow rate increases. The adenosine A1 selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine, did not affect flow rate increases during hypercapnic acidosis. SCH 58261 (5-amino-7-(2-phenyl ethyl)-2-(2-furyl)pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine, a selective adenosine A2A receptor antagonist, blocked the increases in coronary flow rate evoked by metabolic acidosis. An adenosine transport inhibitor, dipyridamole, doubled coronary flow rates during hypercapnic acidosis. When taken in conjunction with previous reports that acidosis enhances adenosine release from cardiac preparations, these results suggest that adenosine is a significant contributor to acidosis-evoked increases in coronary flow.
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA. jphillis@med.wayne.edu
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Phillis
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Song
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O'Regan
D000138:Acidosis / Q000503:physiopathology*; D000142:Acidosis, Respiratory / Q000503:physiopathology*; D000241:Adenosine / Q000502:physiology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D006935:Hypercapnia / Q000188:drug therapy; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D002110:Caffeine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine