Combined NO and PG inhibition augments alpha-adrenergic vasoconstriction in contracting human skeletal muscle.
Sympathetic alpha-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 alpha-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 N(G)-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 alpha1-agonist), and clonidine (an alpha2-agonist) were significantly blunted during exercise compared with adenosine treatment. After combined inhibition of NO and PGs, the vasoconstrictor responses to all alpha-adrenergic receptor stimuli were augmented by approximately 10% in contracting muscle (P <0.05), whereas the responses to phenylephrine and clonidine were also augmented by approximately 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 alpha-adrenergic vasoconstriction in contracting muscle but does not completely restore the vasoconstrictor responses compared with those observed during passive vasodilation in resting muscle.
Dinenno
Frank A
FA
Dept. of Health and Exercise Science, Colorado State Univ., 220 Moby-B Complex, Fort Collins, CO 80523-1582, USA. fdinenno@cahs.colostate.edu
Joyner
Michael J
MJ
D000241:Adenosine / Q000008:administration & dosage; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000008:administration & dosage; D006801:Humans; D008297:Male; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000294:innervation / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010656:Phenylephrine / Q000008:administration & dosage; D011453:Prostaglandins / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology; D014439:Tyramine / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D011453:Prostaglandins; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D009569:Nitric Oxide; D000241:Adenosine; D003000:Clonidine; D009638:Norepinephrine; D014439:Tyramine