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Effects of nitric oxide synthase inhibition by l ‐NAME on oxygen uptake kinetics in isolated canine muscle in situ
Author(s) -
Grassi Bruno,
Hogan Michael C.,
Kelley Kevin M.,
Howlett Richard A.,
Gladden L. Bruce
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.090068
Subject(s) - chemistry , phosphocreatine , nitric oxide synthase , vasodilation , contraction (grammar) , nitric oxide , medicine , kinetics , endocrinology , muscle contraction , biophysics , biology , physics , quantum mechanics , energy metabolism
Nitric oxide (NO) has an inhibitory action on O 2 uptake at the level of the mitochondrial respiratory chain. The aim of this study was to evaluate the effects of NO synthase (NOS) inhibition on muscle kinetics. Isolated canine gastrocnemius muscles in situ ( n = 6) were studied during transitions from rest to 4‐min of electrically stimulated contractions corresponding to ∼60% of the muscle peak . Two conditions were compared: (i) Control (CTRL) and (ii) l ‐NAME, in which the NOS inhibitor l ‐NAME (20 mg kg −1 ) was administered. In both conditions the muscle was pump‐perfused with constantly elevated blood flow , at a level measured during a preliminary contraction trial with spontaneous self‐perfused. A vasodilatory drug was also infused. Arterial and venous O 2 concentrations were determined at rest and at 5–7 s intervals during the transition. was calculated by Fick's principle. Muscle biopsies were obtained at rest and during contractions. Muscle force was measured continuously. Phosphocreatine hydrolysis and the calculated substrate level phosphorylation were slightly (but not significantly) lower in l ‐NAME than in CTRL. Significantly ( P < 0.05) less fatigue was found in l ‐NAME versus CTRL. The time delay (TD f ) and the time constant (τ f ) of the ‘fundamental’ component of kinetics were not significantly different between CTRL (TD f 7.2 ± 1.2 s; and τ f 10.6 ± 1.3, ± s.e.m. ) and l ‐NAME (TD f 9.3 ± 0.6; and τ f 10.4 ± 1.0). Contrary to our hypothesis, NOS inhibition did not accelerate muscle kinetics. The down‐regulation of mitochondrial respiration by NO does not limit the kinetics of adjustment of oxidative metabolism at exercise onset.