title: Effect of cystamine on blood pressure and vascular characteristics in spontaneously hypertensive rats.
abstract: BACKGROUND
  Tissue transglutaminase (t-TG) has been implicated in small artery remodelling. The aim of this study was to determine if cystamine, an inhibitor of t-TG, could reduce blood pressure in spontaneously hypertensive rats (SHR) and if so to what extent this is mediated through small arteries.
  
  
  METHODS
  In vitro inhibition of t-TG, with cystamine, was studied in organ culture and wire myograph setups in small mesenteric arteries obtained from SHR. In vivo treatment with cystamine (80 mg/kg/day) or amlodipine (10 mg/kg/day) was performed with osmotic pumps in adult SHR, and hemodynamic parameters determined with telemetry. Plasma concentrations of cystamine were determined with a liquid chromatography setup. Small arteries were harvested following administration of cystamine, and structural as well as functional characteristics were determined.
  
  
  RESULTS
  SHR small arteries showed inward remodelling following in vitro activation. Administration of cystamine caused attenuation of the inward remodelling induced by activation. In vivo administration of cystamine caused a 9 ± 2 mm Hg reduction in blood pressure, but with no detectable alterations in small artery structure.
  
  
  CONCLUSIONS
  t-TG is potentially involved in vascular remodelling of SHR small arteries and results support a possible role for t-TG in blood pressure control.
authors.affiliation: Department of Pharmacology, University of Aarhus, Aarhus, Denmark. Morten.engholm.pedersen @ farm.au.dk
authors.forename: M
authors.initials: M
authors.lastname: Engholm
authors.forename: A
authors.initials: A
authors.lastname: Eftekhari
authors.forename: G
authors.initials: G
authors.lastname: Chwatko
authors.forename: E
authors.initials: E
authors.lastname: Bald
authors.forename: M J
authors.initials: MJ
authors.lastname: Mulvany
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003538:Cystamine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051381:Rats; D011918:Rats, Inbred SHR; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D017311:Amlodipine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D003538:Cystamine