Phosphodiesterase-5 inhibition preserves exercise-onset vasodilator kinetics when NOS activity is reduced

J. Mikhail Kellawan, Jacqueline K. Limberg, Zachariah M. Scruggs, Wayne T. Nicholson, William G. Schrage, Michael Joseph Joyner, Timothy B Curry

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Nitricoxide (NO)-mediated vasodilation contributes to the rapid rise in muscle blood flow at exercise onset. This occurs via increased cyclic guanos-ine monophosphate (cGMP), which is catabolized by phosphodiesterase-5 (PDE-5). Whether PDE-5 limits exercise vasodilation onset kinetics is unknown. We hypothesized the time course of exercise vasodilation would be 1) accelerated during PDE-5 inhibition (sildenafil citrate, SDF) and 2) decelerated during NO synthase inhibition (N G-monomethyl-L-arginine, L-NMMA), and 3) the effect of SDF on vasodilation onset kinetics would be attenuated with concurrent L-NMMA. Data from 29 healthy adults were analyzed. Individuals completed 5 min of moderate-intensity forearm exercise under control conditions and during 1) oral SDF (n = 8), 2) intra-arterial L-NMMA (n = 15), or 3) combined SDF + L-NMMA (n = 6). Forearm blood flow (FBF; Doppler ultrasound of the brachial artery) and mean brachial artery blood pressure (MAP) were measured continuously. Forearm vascular conductance (FVC, FBF ÷ MAP) was curve-fit with a monoexponential model, and vasodilation onset kinetics were assessed by mean response time (MRT, time to achieve 63% of steady state). SDF had no effect on MRT (P = 0.90). NOS inhibition increased MRT (P = 0.01). MRT during SDF+L-NMMA was not different from control exercise (P = 0.76). PDE-5 inhibition alone has no effect on rapid-onset vasodilation. Whereas NOS inhibition decelerates vasodilator kinetics, when combined with SDF, vasodilator kinetics do not differ from control. These data suggest NO-indepen-dent activation of cGMP occurs at exercise onset; thus PDE-5 inhibition may improve vasodilation in pathologies where NO bioavailability is impaired.

Original languageEnglish (US)
Pages (from-to)276-282
Number of pages7
JournalJournal of Applied Physiology
Volume124
Issue number2
DOIs
StatePublished - Feb 1 2018

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Type 5 Cyclic Nucleotide Phosphodiesterases
Vasodilator Agents
Vasodilation
omega-N-Methylarginine
Exercise
Forearm
Brachial Artery
Doppler Ultrasonography
Sildenafil Citrate
Inhibition (Psychology)
Biological Availability
Reaction Time
Blood Vessels
Arginine
Pathology
Blood Pressure
Muscles

Keywords

  • Cyclic GMP
  • Exercise onset
  • Nitric oxide
  • Sildenafil

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Phosphodiesterase-5 inhibition preserves exercise-onset vasodilator kinetics when NOS activity is reduced. / Kellawan, J. Mikhail; Limberg, Jacqueline K.; Scruggs, Zachariah M.; Nicholson, Wayne T.; Schrage, William G.; Joyner, Michael Joseph; Curry, Timothy B.

In: Journal of Applied Physiology, Vol. 124, No. 2, 01.02.2018, p. 276-282.

Research output: Contribution to journalArticle

Kellawan, J. Mikhail ; Limberg, Jacqueline K. ; Scruggs, Zachariah M. ; Nicholson, Wayne T. ; Schrage, William G. ; Joyner, Michael Joseph ; Curry, Timothy B. / Phosphodiesterase-5 inhibition preserves exercise-onset vasodilator kinetics when NOS activity is reduced. In: Journal of Applied Physiology. 2018 ; Vol. 124, No. 2. pp. 276-282.
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