Effect of adenosine receptor blockade with caffeine on sympathetic response to handgrip exercise in heart failure.
Adenosine (Ado) increases muscle sympathetic nerve activity (MSNA) reflexively. Plasma Ado and MSNA are elevated in heart failure (HF). We tested the hypothesis that Ado receptor blockade by caffeine would attenuate reflex MSNA responses to handgrip (HG) and posthandgrip ischemia (PHGI) and that this action would be more prominent in HF subjects than in normal subjects. We studied 12 HF subjects and 10 age-matched normal subjects after either saline or caffeine (4 mg/kg) infusion during isometric [30% of maximal voluntary contraction (MVC)] and isotonic (10%, 30%, and 50%) HG exercise, followed by 2 min of PHGI. In normal subjects, caffeine did not block increases in MSNA during PHGI after 50% HG. In HF subjects, caffeine abolished MSNA responses to PHGI after both isometric and 50% isotonic exercise (P < 0.05) but MSNA responses during HG were unaffected. These findings are consistent with muscle metaboreflex stimulation by endogenous Ado during ischemic or intense nonischemic HG in HF and suggest an important sympathoexcitatory role for endogenous Ado during exercise in this condition.
Notarius
C F
CF
Division of Cardiology, Toronto General and Mount Sinai Hospitals, University of Toronto, Toronto, Ontario, Canada.
Atchison
D J
DJ
Rongen
G A
GA
Floras
J S
JS
D000241:Adenosine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002110:Caffeine / Q000097:blood / Q000494:pharmacology*; D005080:Exercise Test; D005260:Female; D018737:Hand Strength; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007511:Ischemia / Q000503:physiopathology; D007537:Isometric Contraction / Q000187:drug effects; D007551:Isotonic Contraction / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D058915:Purinergic P1 Receptor Antagonists; D012018:Reflex / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology*
D058915:Purinergic P1 Receptor Antagonists; D002110:Caffeine; D000241:Adenosine