title: The actions of Shiga toxin-2 administration into the brain on renal sympathetic nerve activity.
abstract: BACKGROUND
  It remains unclear whether Shiga toxin-2 (Stx-2)-induced acute encephalopathy contributes to an inappropriate activation of the renal sympathetic outflow. This investigation set out to examine the impact of Stx-2 administered into the brain on the neural control of the kidney.
  
  
  METHODS
  Using acutely anaesthetised male Wistar rats (300-350 g), saline, Stx-2 (10 μg/kg) or lipopolysaccharide (LPS 50 μg/kg) was administered intracerebroventricularly (icv) and measurements of renal haemodynamic and excretory function or renal nerve activity were made over the following 4 h.
  
  
  RESULTS
  There were minimal changes in renal blood flow, glomerular filtration rate, urine flow or sodium excretion, irrespective of whether saline, Stx-2 or LPS was administered into the brain. The renal nerve recordings showed that whereas saline and LPS caused small inconsistent changes in renal nerve activity over the 4-h period, there was a significant (P < 0.05) doubling of renal nerve activity in the rats which were administered Stx-2 icv. Immunocytochemical examination demonstrated that Stx-2 induced globotriaosylceramide receptors, the proposed functional receptors for Stx-2, on the blood vessel walls around the hypothalamus and hippocampus, and histological evaluations showed that changes in the kidney were beginning to occur to the renal tubular epithelial cells, consistent with developing lesions.
  
  
  CONCLUSIONS
  Stx-2 crosses either the blood-brain barrier or the blood-cerebrospinal fluid barrier where it can alter neuronal function and trigger neuronal derangements. These structural changes could contribute, at least in part, to the raised renal sympathetic nerve activity.
authors.affiliation: Department of Paediatrics, School of Medicine, Teikyo University, Tokyo, Japan. akio@med.teikyo-u.ac.jp
authors.forename: Akio
authors.initials: A
authors.lastname: Nakamura
authors.forename: Akira
authors.initials: A
authors.lastname: Imaizumi
authors.forename: Takao
authors.initials: T
authors.lastname: Kohsaka
authors.forename: Chunlong
authors.initials: C
authors.lastname: Huang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Huang
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Johns
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000502:physiology; D007276:Injections, Intraventricular; D007668:Kidney / Q000187:drug effects / Q000294:innervation* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D022641:Shiga Toxin 2 / Q000633:toxicity*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides; D022641:Shiga Toxin 2