Role of adenosine in vasodilation of epimyocardial coronary microvessels during reduction in perfusion pressure.
Previous studies in which an isolated heart or in situ constant pressure preparation was used suggested a minimal role for adenosine in autoregulatory control of coronary circulation. These results, however, are controversial, and the role of adenosine in autoregulation of flow in heart is uncertain. To test the hypothesis that adenosine mediates microvascular dilation in response to reduction in perfusion pressure (PP), we performed experiments in 41 open-chest chloralose-anesthetized dogs. Internal diameters (ID) of epicardial small arterioles < 100 mumol were measured with an intravital microscope and stroboscopic epiillumination synchronized to cardiac cycle. PP was reduced by graded stenoses of the left anterior descending coronary artery (LAD, mild stenosis PP = 60 mm Hg; critical stenosis PP = 40 mm Hg) and complete occlusion. 8-Phenyltheophylline (8-PT 10 microM) or adenosine deaminase (ADA 10 U/min) was topically superfused onto the heart. Arteriolar dilation induced by topically applied adenosine < or = 10 microM was completely blocked by 8-PT. Without 8-PT (vehicle group), mild critical stenosis and complete occlusion caused arteriolar dilation (percentage of change in diameter 8.6 +/- 2.6, 16.0 +/- 2.7, and 13.6 +/- 4.8%). 8-PT did not inhibit this dilation (8.5 +/- 2.8, 16.1 +/- 4.6, 15.1 +/- 5.7%, NS vs. vehicle group). Topically applied ADA significantly inhibited intravenously (i.v.) administered adenosine-induced arteriolar dilation. Without ADA, arteriolar dilation occurred (16.6 +/- 3.0, 28.2 +/- 4.3, 15.4 +/- 6.2%, at each PP). However, ADA did not inhibit dilation induced by gradual stenoses (10.6 +/- 1.4, 24.2 +/- 4.3, 17.5 +/- 6.9%, at each PP, NS vs. vehicle group).(ABSTRACT TRUNCATED AT 250 WORDS)
Komaru
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Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242.
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D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000008:administration & dosage / Q000494:pharmacology*; D000287:Administration, Topical; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007260:Infusion Pumps; D008297:Male; D011312:Pressure; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D013806:Theophylline; C028322:8-phenyltheophylline; D000243:Adenosine Deaminase; D000241:Adenosine