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The effect of nitric oxide synthase inhibition with and without inhibition of prostaglandins on blood flow in different human skeletal muscles

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Purpose: Animal studies suggest that the inhibition of nitric oxide synthase (NOS) affects blood flow differently in different skeletal muscles according to their muscle fibre type composition (oxidative vs glycolytic). Quadriceps femoris (QF) muscle consists of four different muscle parts: vastus intermedius (VI), rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) of which VI is located deep within the muscle group and is generally regarded to consist mostly of oxidative muscle fibres. Methods: We studied the effect of NOS inhibition on blood flow in these four different muscles by positron emission tomography in eight young healthy men at rest and during one-leg dynamic exercise, with and without combined blockade with prostaglandins. Results: At rest blood flow in the VI (2.6 ± 1.1 ml/100 g/min) was significantly higher than in VL (1.9 ± 0.6 ml/100 g/min, p = 0.015) and RF (1.7 ± 0.6 ml/100 g/min, p = 0.0015), but comparable to VM (2.4 ± 1.1 ml/100 g/min). NOS inhibition alone or with prostaglandins reduced blood flow by almost 50% (p < 0.001), but decrements were similar in all four muscles (drug × muscle interaction, p = 0.43). During exercise blood flow was also the highest in VI (45.4 ± 5.5 ml/100 g/min) and higher compared to VL (35.0 ± 5.5 ml/100 g/min), RF (38.4 ± 7.4 ml/100 g/min), and VM (36.2 ± 6.8 ml/100 g/min). NOS inhibition alone did not reduce exercise hyperemia (p = 0.51), but combined NOS and prostaglandin inhibition reduced blood flow during exercise (p = 0.002), similarly in all muscles (drug × muscle interaction, p = 0.99). Conclusion: NOS inhibition, with or without prostaglandins inhibition, affects blood flow similarly in different human QF muscles both at rest and during low-to-moderate intensity exercise.
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Eur J Appl Physiol (2017) 117:1175–1180
DOI 10.1007/s00421-017-3604-2
ORIGINAL ARTICLE
The effect ofnitric oxide synthase inhibition withandwithout
inhibition ofprostaglandins onblood flow indifferent human
skeletal muscles
IlkkaHeinonen1,2,3 · BengtSaltin5· YlvaHellsten4· KariK.Kalliokoski1
Received: 22 November 2016 / Accepted: 22 March 2017 / Published online: 21 April 2017
© Springer-Verlag Berlin Heidelberg 2017
in VL (1.9 ± 0.6 ml/100 g/min, p = 0.015) and RF
(1.7±0.6ml/100g/min, p=0.0015), but comparable to
VM (2.4 ± 1.1 ml/100 g/min). NOS inhibition alone or
with prostaglandins reduced blood flow by almost 50%
(p<0.001), but decrements were similar in all four mus-
cles (drug×muscle interaction, p=0.43). During exercise
blood flow was also the highest in VI (45.4±5.5ml/100g/
min) and higher compared to VL (35.0 ± 5.5 ml/100 g/
min), RF (38.4 ± 7.4 ml/100 g/min), and VM
(36.2 ± 6.8 ml/100 g/min). NOS inhibition alone did not
reduce exercise hyperemia (p=0.51), but combined NOS
and prostaglandin inhibition reduced blood flow during
exercise (p=0.002), similarly in all muscles (drug×mus-
cle interaction, p=0.99).
Conclusion NOS inhibition, with or without prostaglan-
dins inhibition, affects blood flow similarly in different
human QF muscles both at rest and during low-to-moderate
intensity exercise.
Keywords Muscle fibres· Blood flow· Nitric oxide·
Prostanoids· Exercise· Humans
Abbreviations
NOS Nitric oxide synthase
VI Vastus intermedius
RF Rectus femoris
VM Vastus medialis
VL Vastus lateralis
Introduction
The continuous supply of oxygen via blood is of para-
mount importance for proper function of the muscle,
especially during exercise (Heinonen etal. 2014, 2015;
Abstract
Purpose Animal studies suggest that the inhibition of
nitric oxide synthase (NOS) affects blood flow differently
in different skeletal muscles according to their muscle fibre
type composition (oxidative vs glycolytic). Quadriceps
femoris (QF) muscle consists of four different muscle parts:
vastus intermedius (VI), rectus femoris (RF), vastus media-
lis (VM), and vastus lateralis (VL) of which VI is located
deep within the muscle group and is generally regarded to
consist mostly of oxidative muscle fibres.
Methods We studied the effect of NOS inhibition on
blood flow in these four different muscles by positron emis-
sion tomography in eight young healthy men at rest and
during one-leg dynamic exercise, with and without com-
bined blockade with prostaglandins.
Results At rest blood flow in the VI
(2.6 ± 1.1 ml/100 g/min) was significantly higher than
Communicated by: Keith Phillip George
Bengt Saltin: Deceased.
* Ilkka Heinonen
ilkka.heinonen@utu.fi
1 Turku PET Centre, University ofTurku, PO Box52,
20521Turku, Finland
2 Department ofClinical Physiology andNuclear Medicine,
University ofTurku, Turku, Finland
3 Division ofExperimental Cardiology, Thoraxcenter, Erasmus
MC, University Medical Center Rotterdam, Rotterdam,
TheNetherlands
4 Exercise andSport Sciences, Section ofHuman Physiology,
University ofCopenhagen, Copenhagen, Denmark
5 Copenhagen Muscle Research Center, University
ofCopenhagen, Copenhagen, Denmark
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... The most important functions of nNOS include modulation of synapse plasticity in the central nervous system, central regulation of blood pressure, maintenance of smooth muscle tone of internal organs, in particular by generating NO in nitrergic nerve endings, control of blood supply to skeletal muscle fibers [35,38,44,49,51]. ...
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... However, this view was also challenged in numerous studies in which NO accounted only for a minor part (if any) of the dilation in active hyperemia [4]. In humans, NOS inhibition attenuated blood flow during exercise only in combination with blockade of prostaglandin synthesis indicating a substantial redundancy between these two systems [14], whereas EDH cannot compensate their impairment [28]. ...
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