Document Detail


A role for adenosine in coronary vasoregulation in man. Effects of theophylline and enprofylline.
MedLine Citation:
PMID:  8590556     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adenosine has been suggested to have a role in regulation of the tone of the cardiac resistance vessels. To elucidate the coronary vasoregulatory role of endogenous adenosine in man, we studied the effects of adenosine receptor antagonism by theophylline on coronary blood flow at rest and during light exercise. However, theophylline may also exert pharmacological effects not related to adenosine antagonism. To clarify the contribution of endogenous adenosine in coronary hyperaemia, the effect of theophylline was compared to that of enprofylline, a xanthine which exerts similar pharmacological effects as theophylline while lacking antagonistic action at adenosine receptors. Twenty healthy subjects (10 males) aged 22-39 years were examined. Coronary sinus (CS) blood flow and blood oxygen content were determined at rest and during supine bicycle exercise, at a load of 50 watts, for 10 min. Thereafter, stepwise infusion of adenosine (30 to 60 micrograms/kg/min into the subclavian vein) was performed. Theophylline or enprofylline treatment was instituted randomly and double-blind (10 in each group), and the procedures (i.e. determinations at rest, during exercise and during infusion of adenosine) were repeated. In all 20 subjects, basal CS flow was 70 +/- 6 ml/min and the cardiac oxygen extraction ((A-CS)O2D) was 123 +/- 3 ml/l. During exercise, CS flow and (A-CS)O2D increased to 135 +/- 17 ml/min and 132 +/- 3 ml/l, respectively. Adenosine increased CS flow dose dependently to 161 +/- 27 ml/min, while (A-CS)O2D decreased to 66 +/- 7 ml/l. The vasodilatory effect of adenosine was readily counteracted by theophylline, the increase in CS flow being 33% vs. 133% in the control situation. Enprofylline, on the other hand, enhanced the response to exogenous adenosine. Theophylline, at a dose lacking effect on heart rate and blood pressure, decreased CS flow at rest by 14% (P < 0.05) and during exercise by 18% (P < 0.05). ((A-CS)O2D increased by 14% at rest and during exercise (P < 0.001). Enprofylline, on the other hand, was without effect. The differences in responses between theophylline and enprofylline with respect to coronary flow and oxygen extraction were significant both at rest and during exercise. It is concluded that theophylline increases coronary vascular resistance, while enprofylline, lacking adenosine antagonistic properties, was without such effect. This indicates a physiological role of adenosine in regulation of coronary flow.
Authors:
A Edlund; T Conradsson; A Sollevi
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical physiology (Oxford, England)     Volume:  15     ISSN:  0144-5979     ISO Abbreviation:  Clin Physiol     Publication Date:  1995 Nov 
Date Detail:
Created Date:  1996-03-28     Completed Date:  1996-03-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8309768     Medline TA:  Clin Physiol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  623-36     Citation Subset:  IM    
Affiliation:
Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Adenosine / pharmacology,  physiology*
Adult
Blood Pressure / drug effects
Coronary Circulation / drug effects,  physiology*
Double-Blind Method
Exercise / physiology
Female
Heart / drug effects
Heart Rate / drug effects
Humans
Male
Myocardium / metabolism
Oxygen Consumption / drug effects
Receptors, Purinergic P1 / antagonists & inhibitors
Theophylline / pharmacology*
Vascular Resistance / drug effects
Vasodilator Agents / pharmacology*
Xanthines / pharmacology*
Chemical
Reg. No./Substance:
0/Receptors, Purinergic P1; 0/Vasodilator Agents; 0/Xanthines; 41078-02-8/enprofylline; 58-55-9/Theophylline; 58-61-7/Adenosine

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