title: Involvement of hypothalamic nitric oxide signaling in the modulation of a rat's exercise capacity.
abstract: OBJECTIVE
  The aim of this study was to explore the effect of nitric oxide (NO) in some regions of the hypothalamus on exercise capacity.
  
  
  METHODS
  To assess the role of central NO in exercise capacity, L-arginine (L-Arg, a precursor of NO synthesis), NG-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor), or placebo saline was injected into the lateral cerebral ventricle of rats once a day for 4 consecutive days. Thereafter, an one-time exhaustive treadmill exercise was performed, and the levels of nitrate/nitrite, as a marker of NO production, in blood plasma and hypothalamus were assayed. Neuronal nitric oxide synthase (nNOS)-expressing cells were immunohistochemically stained and analyzed in the paraventricular nucleus (PVN), the dorsomedial hypothalamus (DMH), and the ventromedial hypothalamus. Exercise time to exhaustion and total workload were determined.
  
  
  RESULTS
  Compared with the rats in the saline group, the exercise time to exhaustion and total workload increased 50% in the L-Arg group and decreased 50% in the L-NAME group. The nitrate/nitrite level of hypothalamus in the L-Arg group increased 50% and decreased 29.4% in the L-NAME group. The number of nNOS-positive cells was significantly increased, 56.5%, in PVN and, 119%, in DMH, but not in ventromedial hypothalamus. No significant changes in nNOS-positive cells were found in L-NAME-treated rats.
  
  
  CONCLUSIONS
  These results show that the modulation of hypothalamic NO signaling can affect the rat's running performance during a treadmill exercise and that enhanced NO signaling by induction of nNOS in PVN and DMH plays a role in improving exercise capacity after central administration of L-Arg. NO signaling in PVN and DMH may be a useful target for the pharmacological intervention of exercise performance or capacity.
authors.affiliation: aDepartment of Exercise Science, Institute of Sport and Exercise Medicine, North University of China, Taiyuan bDepartment of Radiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Liu
authors.forename: Jinjuan
authors.initials: J
authors.lastname: Xue
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002408:Catheters, Indwelling; D002452:Cell Count; D002491:Central Nervous System Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005221:Fatigue / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012420:Running / Q000502:physiology*
chemical_list: D002491:Central Nervous System Agents; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D001120:Arginine; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D019331:NG-Nitroarginine Methyl Ester