title: Central fatigue induced by losartan involves brain serotonin and dopamine content.
abstract: OBJECTIVE
  To investigate the influence of angiotensin II (Ang II) AT1 receptors blockade on central fatigue induced by brain content of serotonin (5-HT) and dopamine (DA) during exercise.
  
  
  METHODS
  Losartan (Los) was intracerebroventricularly injected in rats before running until fatigue (n = 6 per group). At fatigue, brains were quickly removed for measurement of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), DA, and 3,4-dihydroxyphenylacetic acid by high-pressure liquid chromatography in the preoptic area, hypothalamus, hippocampus, and frontal cortex.
  
  
  RESULTS
  Intracerebroventricular injection of Los increased 5-HT content in the preoptic area and hypothalamus. Such results correlated positively with body heating rate and inversely with time to fatigue. On the other hand, time to fatigue was directly correlated with the diminished concentration of 5-HT in the hippocampus of Los rats. Although the levels of DA were not affected by Los treatment during exercise in any of the brain areas studied, a higher 5-HT/DA ratio was seen in the hypothalamus of Los animals. This higher hypothalamic 5-HT/DA ratio correlated positively with body heating rate and negatively with time to fatigue.
  
  
  CONCLUSIONS
  Our results show that central fatigue due to hyperthermia and increased body heating rate induced by central Ang II AT1 receptor blockade in exercising rats is related with higher 5-HT content in the preoptic area and hypothalamus as well as with decreased levels of this neurotransmitter in the hippocampus. Furthermore, the interaction between 5-HT and DA within the hypothalamus seems to contribute to hyperthermia and premature central fatigue after angiotensinergic inhibition.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil.
authors.forename: Laura H R
authors.initials: LH
authors.lastname: Leite
authors.forename: Alex G
authors.initials: AG
authors.lastname: Rodrigues
authors.forename: Danusa D
authors.initials: DD
authors.lastname: Soares
authors.forename: Umeko
authors.initials: U
authors.lastname: Marubayashi
authors.forename: Cândido C
authors.initials: CC
authors.lastname: Coimbra
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D005221:Fatigue / Q000139:chemically induced / Q000378:metabolism*; D005625:Frontal Lobe / Q000737:chemistry / Q000187:drug effects; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D010805:Physical Conditioning, Animal; D011301:Preoptic Area / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D019808:Losartan; D004298:Dopamine