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Muscle Metaboreflex‐Induced Vasoconstriction of Ischemic Active Muscle is Exaggerated in Heart Failure
Author(s) -
Kaur Jasdeep,
Alvarez Alberto,
Hanna Hanna W.,
Machado Tiago M.,
Senador Danielle,
Krishnan Abhinav C.,
Altamimi Yasir H.,
O'Leary Donal S.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1286.6
Subject(s) - vasoconstriction , vasodilation , medicine , hindlimb , cardiology , vascular resistance , blood flow , skeletal muscle , blood pressure , heart failure , cardiac output , anesthesia
When oxygen delivery to active muscle is insufficient to meet metabolic demands, metabolites accumulate and stimulate skeletal muscle afferents inducing a reflex increase in blood pressure, termed the muscle metaboreflex. Muscle metaboreflex activation during submaximal dynamic exercise increases arterial pressure predominantly via an increase in cardiac output, as little peripheral vasoconstriction occurs. In heart failure, increases in cardiac output are limited and the mechanisms mediating the metaboreflex‐induced pressor response shift to mainly peripheral vasoconstriction. We recently demonstrated that muscle metaboreflex activation induces sympathetic vasoconstriction in the ischemic active muscle, which limits the ability of the metaboreflex to restore blood flow (Kaur et. al., Am J Physiol Heart Circ 2015). In the present study we tested the hypothesis that this vasoconstriction in the ischemic muscle is exaggerated in heart failure. Changes in hindlimb vascular resistance (calculated as femoral arterial pressure/hindlimb blood flow) were observed during metaboreflex activation (induced via graded reductions in hindlimb blood flow during mild exercise) in the same animals with and without α 1 ‐adrenergic blockade (prazosin; 50 μg/kg) and before and after the induction of heart failure. Thus, each animal was observed in each state and served as its own control. During mild exercise, hindlimb skeletal muscle blood flow must be reduced below a clear threshold before the metaboreflex is engaged. In normal animals, initial flow reductions caused metabolic vasodilation. However, when blood flow was reduced below the metaboreflex threshold, vasoconstriction in the ischemic muscle occurred. In normal animals, α 1 ‐adrenergic blockade did not markedly affect hindlimb blood flow or vascular resistance during exercise however, the metaboreflex‐induced vasoconstriction was abolished indicating that this vasoconstriction was neurogenic. After induction of heart failure, hindlimb blood flow during exercise was reduced by < 20% and hindlimb vascular resistance was substantially elevated. Metaboreflex‐induced vasoconstriction within the ischemic muscle was exaggerated after induction of heart failure. In heart failure, α 1 ‐adrenergic blockade caused substantial hindlimb vasodilation during exercise restoring blood flow to near normal levels. Metaboreflex‐induced vasoconstriction was abolished after α 1 ‐adrenergic blockade. We conclude that in heart failure the ability of muscle metaboreflex to restore blood flow to the ischemic muscle is impaired and this may contribute to exercise intolerance. Support or Funding Information NIH‐HL55473