Effect of cystamine on blood pressure and vascular characteristics in spontaneously hypertensive rats

J Vasc Res. 2011;48(6):476-84. doi: 10.1159/000327773. Epub 2011 Jul 20.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / drug effects
  • Adaptation, Physiological / physiology
  • Amlodipine / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure / drug effects*
  • Cystamine / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • GTP-Binding Proteins / antagonists & inhibitors*
  • GTP-Binding Proteins / metabolism
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Male
  • Mesenteric Arteries / drug effects*
  • Mesenteric Arteries / physiology
  • Organ Culture Techniques
  • Protein Glutamine gamma Glutamyltransferase 2
  • Rats
  • Rats, Inbred SHR
  • Transglutaminases / antagonists & inhibitors*
  • Transglutaminases / metabolism

Substances

  • Antihypertensive Agents
  • Enzyme Inhibitors
  • Amlodipine
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins
  • Cystamine