Document Detail

Role of adenosine in the sympathetic activation produced by isometric exercise in humans.
MedLine Citation:
PMID:  8163667     Owner:  NLM     Status:  MEDLINE    
Isometric exercise increases sympathetic nerve activity and blood pressure. This exercise pressor reflex is partly mediated by metabolic products activating muscle afferents (metaboreceptors). Whereas adenosine is a known inhibitory neuromodulator, there is increasing evidence that it activates afferent nerves. We, therefore, examined the hypothesis that adenosine stimulates muscle afferents and participates in the exercise pressor reflex in healthy volunteers. Intraarterial administration of adenosine into the forearm, during venous occlusion to prevent systemic effects, mimicked the response to exercise, increasing muscle sympathetic nerve activity (MSNA, lower limb microneurography) and mean arterial blood pressure (MABP) at all doses studied (2, 3, and 4 mg). Heart rate increased only with the highest dose. Intrabrachial adenosine (4 mg) increased MSNA by 96 +/- 25% (n = 6, P < 0.01) and MABP by 12 +/- 3 mmHg (P < 0.01). Adenosine produced forearm discomfort, but equivalent painful stimuli (forearm ischemia and cold exposure) increased MSNA significantly less than adenosine. Furthermore, adenosine receptor antagonism with intrabrachial theophylline (1 microgram/ml forearm per min) blocked the increase in MSNA (92 +/- 15% vs. 28 +/- 6%, n = 7, P < 0.01) and MABP (38 +/- 6 vs. 27 +/- 4 mmHg, P = 0.01) produced by isometric handgrip (30% of maximal voluntary contraction) in the infused arm, but not the contralateral arm. Theophylline did not prevent the increase in heart rate produced by handgrip, a response mediated more by central command than muscle afferent activation. We propose that endogenous adenosine contributes to the activation of muscle afferents involved in the exercise pressor reflex in humans.
F Costa; I Biaggioni
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  93     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1994 Apr 
Date Detail:
Created Date:  1994-05-20     Completed Date:  1994-05-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1654-60     Citation Subset:  AIM; IM; S    
Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232-2195.
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MeSH Terms
Adenosine / pharmacology*
Blood Pressure / drug effects
Dose-Response Relationship, Drug
Muscles / drug effects,  innervation*
Reflex / drug effects
Sympathetic Nervous System / drug effects*,  physiology
Theophylline / pharmacology
Grant Support
Reg. No./Substance:
58-55-9/Theophylline; 58-61-7/Adenosine

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