Effect of adenosine receptor blockade with caffeine on sympathetic response to handgrip exercise in heart failure

Adenosine (Ado) increases muscle sympathetic nerve activity (MSNA) reflexiv ely. Plasma Ado and MSNA are elevated in heart failure (HF). We tested the hypothesis that Ado receptor blockade by caffeine would attenuate reflex MS NA responses to handgrip (HG) and posthandgrip ischemia (PHGI) and that thi s action would be more prominent in HF subjects than in normal subjects. We studied 12 HIP subjects and 10 age-matched normal subjects after either sa line or caffeine (4 mg/kg) infusion during isometric [30% of maximal volunt ary contraction (MVC)] and isotonic (10%, 30%, and 50%) HG exercise, follow ed by 2 min of PHGI. In normal subjects, caffeine did not block increases i n MSNA during PHGI after 50% HG. In HF subjects, caffeine abolished MSNA re sponses to PHGI after both isometric and 50% isotonic exercise (P < 0.05) b ut MSNA responses during HG were unaffected. These findings are consistent with muscle metaboreflex stimulation by endogenous Ado during ischemic or i ntense nonischemic HG in HIP and suggest an important sympathoexcitatory ro le for endogenous Ado during exercise in this condition.