title: Defective endogenous nitric oxide-mediated modulation of cellular respiration in canine skeletal muscle after the development of heart failure.
abstract: BACKGROUND
  It is well documented that nitric oxide (NO) suppresses the function of a number of mitochondrial enzymes. Our recent studies found that endogenous NO may play an important role in the modulation of tissue oxygen (O2) consumption and cellular respiration both in vitro and in vivo.
  
  
  METHODS
  Tissue O2 consumption was measured by a Clark-type O2 electrode at 37 degrees C in freshly isolated skeletal muscle segments from the accessory head of the triceps brachii (90% type I muscle fiber) and extensor carpi radialis (86% type II muscle fiber) from normal dogs and dogs with tachycardia-induced heart failure.
  
  
  RESULTS
  S-nitroso-N-acetylpenicillamine (SNAP), carbachol, and bradykinin at doses of 10(-7) to 10(-4) mol/L concentration significantly suppressed tissue O2 consumption both in the absence and presence of 2,4-dinitrophenol (1 mmol/L), a mitochondrial uncoupler. These effects were not significantly different in the accessory head of the triceps brachii (90% type I muscle fiber) and extensor carpi radialis (86% type II muscle fiber). The effects of carbachol and bradykinin but not SNAP were attenuated by NG-nitro-L-arginine (10(-4) mol/L), indicating inhibition of the formation of endogenous NO. The inhibitory effect on tissue O2 consumption in response to carbachol and bradykinin became significantly smaller in skeletal muscle from dogs with pacing-induced heart failure, but the effects of SNAP were unchanged.
  
  
  CONCLUSIONS
  Endogenous NO released from microvascular endothelium may play an important physiologic role in the modulation of cellular respiration in skeletal muscle, and the loss of this regulatory function may contribute to peripheral metabolic disorders and poor exercise tolerance during heart failure.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla 10595, USA.
authors.forename: W
authors.initials: W
authors.lastname: Shen
authors.forename: M S
authors.initials: MS
authors.lastname: Wolin
authors.forename: T H
authors.initials: TH
authors.lastname: Hintze
mesh_terms: D019297:2,4-Dinitrophenol / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D019069:Cell Respiration / Q000502:physiology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D017079:Exercise Tolerance / Q000502:physiology; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D008659:Metabolic Diseases / Q000209:etiology; D008931:Mitochondria, Muscle / Q000201:enzymology; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D010396:Penicillamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D013610:Tachycardia / Q000150:complications; D014475:Uncoupling Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D014475:Uncoupling Agents; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D002217:Carbachol; D010396:Penicillamine; D019297:2,4-Dinitrophenol; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester