title: Blockage of the afferent sensitive pathway prevents sympathetic atrophy and hemodynamic alterations in rat portal hypertension.
abstract: OBJECTIVE
  Portal hypertension causes arterial vasodilation and sympathetic atrophy in the splanchnic area. We aimed to demonstrate a relationship between hemodynamic alterations and sympathetic atrophy by investigating a pathway from sensitive afferent signals to mesenteric sympathetic ganglia.
  
  
  METHODS
  Experiments were conducted in sham and portal vein ligated (PVL) adult and neonatal rats treated with vehicle or capsaicin. Hemodynamic parameters, and immunohistochemistry, immunofluorescence and Western blot of different tissues were analysed.
  
  
  RESULTS
  cFos expression in the brain supraoptic nuclei was used to confirm abrogation of the afferent signal in capsaicin-treated PVL rats (effectively afferent blocked). Neonatal and adult PVL afferent blocked rats showed simultaneous prevention of hemodynamic alterations and sympathetic atrophy (measured by tyrosine hydroxylase expression in nerve structures of splanchnic vasculature). Not effectively afferent blocked rats showed none of these effects, behaving as PVL vehicle. All capsaicin treated animals presented loss of calcitonin gene-related peptide in superior mesenteric artery and ganglia, whereas neuronal nitric oxide synthase remained unaffected. Neuronal markers semaphorin-3A, nerve growth factor, its precursor and p75 neurotrophic receptor, were significantly over-expressed in the PVL sympathetic ganglia compared with sham, but not in effectively afferent blocked rats. Semaphorin-3A staining in mesenteric ganglia co-localized with vesicular acetylcholine transporter, but not with adrenergic, nitrergic and sensory axons, suggesting that semaphorin-3A might originate in preganglionic neurons.
  
  
  CONCLUSIONS
  These results indicate that the nervous system has a central role in the genesis of the circulatory abnormalities of portal hypertension, and support that mesenteric sympathetic atrophy contributes to splanchnic arterial vasodilation.
authors.affiliation: Liver Unit-Department of Internal Medicine, Hepatic Disease Laboratory, Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Nahia
authors.initials: N
authors.lastname: Ezkurdia
authors.forename: Mar
authors.initials: M
authors.lastname: Coll
authors.forename: Imma
authors.initials: I
authors.lastname: Raurell
authors.forename: Sarai
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Silvia
authors.initials: S
authors.lastname: Cuenca
authors.forename: Antonio
authors.initials: A
authors.lastname: González
authors.forename: Jaime
authors.initials: J
authors.lastname: Guardia
authors.forename: Rafael
authors.initials: R
authors.lastname: Esteban
authors.forename: Joan
authors.initials: J
authors.lastname: Genescà
authors.forename: María
authors.initials: M
authors.lastname: Martell
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D001342:Autonomic Nervous System Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D004195:Disease Models, Animal; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D011169:Portal Vein; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000502:physiology; D013495:Supraoptic Nucleus / Q000473:pathology / Q000503:physiopathology; D014664:Vasodilation / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D016760:Proto-Oncogene Proteins c-fos; D018689:Sensory System Agents; C013090:ligatin; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin