Engholm M, Eftekhari A, Chwatko G, Bald E, Mulvany M J
Department of Pharmacology, University of Aarhus, Aarhus, Denmark. Morten.engholm.pedersen @ farm.au.dk
J Vasc Res. 2011;48(6):476-84. doi: 10.1159/000327773. Epub 2011 Jul 20.
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.
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.
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.
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.
组织转谷氨酰胺酶（t-TG）与小动脉重塑有关。本研究的目的是确定t-TG抑制剂胱胺是否能降低自发性高血压大鼠（SHR）的血压，以及如果能降低，这种作用在多大程度上是通过小动脉介导的。
在从SHR获取的肠系膜小动脉的器官培养和线肌描记装置中，研究胱胺对t-TG的体外抑制作用。在成年SHR中，用渗透泵对胱胺（80毫克/千克/天）或氨氯地平（10毫克/千克/天）进行体内治疗，并用遥测技术测定血流动力学参数。用液相色谱装置测定血浆胱胺浓度。在给予胱胺后采集小动脉，并测定其结构和功能特征。
体外激活后，SHR小动脉出现内向重塑。给予胱胺可减轻激活诱导的内向重塑。体内给予胱胺可使血压降低9±2毫米汞柱，但小动脉结构无明显改变。
t-TG可能参与SHR小动脉的血管重塑，研究结果支持t-TG在血压控制中可能发挥的作用。
