Combined NO and PG inhibition augments α-adrenergic vasoconstriction in contracting human skeletal muscle

Frank A. Dinenno, Michael J. Joyner

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Sympathetic α-adrenergic vasoconstrictor responses are blunted in the vascular beds of contracting muscle (functional sympatholysis). We tested the hypothesis that combined inhibition of nitric oxide (NO) and prostaglandins (PGs) restores sympathetic vasoconstriction in contracting human muscle. We measured forearm blood flow via Doppler ultrasound and calculated the reduction in forearm vascular conductance in response to α-adrenergic receptor stimulation during rhythmic handgrip exercise (6.4 kg) and during a control nonexercise vasodilator condition (using intra-arterial adenosine) before and after combined local inhibition of NO synthase (NOS; via NG-nitro-L- arginine methyl ester) and cyclooxygenase (via ketorolac) in healthy men. Before combined inhibition of NO and PGs, the forearm vasoconstrictor responses to intra-arterial tyramine (which evoked endogenous noradrenaline release), phenylephrine (a selective α1-agonist), and clonidine (an α2-agonist) were significantly blunted during exercise compared with adenosine treatment. After combined inhibition of NO and PGs, the vasoconstrictor responses to all α-adrenergic receptor stimuli were augmented by ∼10% in contracting muscle (P < 0.05), whereas the responses to phenylephrine and clonidine were also augmented by ∼10% during passive vasodilation in resting muscle (P < 0.05). In six additional subjects, PG inhibition alone did not alter the vasoconstrictor responses in resting or contracting muscles. Thus in light of our previous findings, it appears that inhibition of either NO or PGs alone does not affect functional sympatholysis in healthy humans. However, the results from the present study indicate that combined inhibition of NO and PGs augments α-adrenergic vasoconstriction in contracting muscle but does not completely restore the vasoconstrictor responses compared with those observed during passive vasodilation in resting muscle.

Original languageEnglish (US)
Pages (from-to)H2576-H2584
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number6 56-6
DOIs
StatePublished - Dec 1 2004

Keywords

  • Blood flow
  • Exercise
  • Nitric oxide
  • Prostaglandin
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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