Adenosine receptor blockade with 8-p-sulfophenyltheophylline aggravates coronary constriction.
We examined the role of adenosine in modulating the coronary constrictor effect of neuropeptide Y (NPY). Anesthetized dogs (n = 22) were instrumented to record hemodynamics and to collect arterial and coronary venous blood. In control dogs (n = 7), during the first 30 min before NPY, baseline coronary resistance fell slightly. By 10 min after NPY (42 nmol over 4 min), coronary resistance was increased by 30% and fell slowly to pre-NPY levels over the ensuing hour. Intravenous (7.5 mg/kg, n = 3) or intracoronary (to 100 microM arterial concentration, n = 12) infusion of 8-p-sulfophenyltheophylline (8-THEO) blocked the vasodilator effects of adenosine but did not alter the peak dilation seen with papaverine or reactive hyperemia. Over 30 min before NPY, infusion of 8-THEO increased baseline resistance by 31% as it reduced coronary blood flow, despite no change in other hemodynamic parameters or myocardial oxygen consumption. The coronary constrictor effect of NPY was magnified in the presence of adenosine receptor blockade. At 3 min, coronary resistance was increased by 34%, at 5 min by 52%, and at 10 min by 59%. The effect of adenosine receptor blockade on constriction due to NPY could not be attributed to a nonspecific alteration in cardiac function or oxygen consumption. In addition, the increase in baseline coronary resistance following receptor blockade correlated with the worsening of the coronary constriction following NPY (r = 0.48, P less than 0.05). Thus it appears that adenosine modulates an imposed constriction of coronary vessels and acts as a "host defense" to restore coronary tone toward normal.
Martin
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Carlyle Fraser Heart Center, Crawford Long Hospital of Emory University, Department of Medicine (Cardiology), Atlanta, Georgia 30365.
Tidmore
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WC
Patterson
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RE
D000241:Adenosine / Q000502:physiology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004285:Dogs; D004357:Drug Synergism; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D009478:Neuropeptide Y; D011983:Receptors, Purinergic; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000241:Adenosine