Effect of Cystamine on Blood Pressure and Vascular Characteristics in Spontaneously Hypertensive Rats

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.