title: Effects of nitric oxide synthase inhibition by L-NAME on oxygen uptake kinetics in isolated canine muscle in situ.
abstract: Nitric oxide (NO) has an inhibitory action on O2 uptake (VO2) 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 (VO2) kinetics. Isolated canine gastrocnemius muscles in situ (n = 6) were studied during transitions from rest to 4-min of electrically stimulated contractions corresponding to approximately 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 (Q), at a level measured during a preliminary contraction trial with spontaneous self-perfused (Q). A vasodilatory drug was also infused. Arterial and venous O2 concentrations were determined at rest and at 5-7 s intervals during the transition. VO2 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 (tau(f)) of the 'fundamental' component of VO2 kinetics were not significantly different between CTRL (TD(f) 7.2 +/- 1.2 s; and tau(f) 10.6 +/- 1.3, +/- s.e.m.) and L-NAME (TD(f) 9.3 +/- 0.6; and tau(f) 10.4 +/- 1.0). Contrary to our hypothesis, NOS inhibition did not accelerate muscle VO2 kinetics. The down-regulation of mitochondrial respiration by NO does not limit the kinetics of adjustment of oxidative metabolism at exercise onset.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Milano, LITA - Via Fratelli Cervi 93, I -20090 Segrate (MI), Italy. bruno.grassi@unimi.it
authors.forename: Bruno
authors.initials: B
authors.lastname: Grassi
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hogan
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Kelley
authors.forename: Richard A
authors.initials: RA
authors.lastname: Howlett
authors.forename: L Bruce
authors.initials: LB
authors.lastname: Gladden
mesh_terms: D000818:Animals; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000502:physiology*; D008297:Male; D008657:Metabolic Clearance Rate; D018482:Muscle, Skeletal / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*
chemical_list: D019001:Nitric Oxide Synthase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester