Time course of vascular arginase expression and activity in spontaneously hypertensive rats
Time course of vascular arginase expression and activity in spontaneously hypertensive rats
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DOI：
10.1016/j.lfs.2006.12.003
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发表时间：
2007-02-27
期刊：
影响因子：
6.1
通讯作者：
Berthelot, Alain
中科院分区：
文献类型：
--
作者：
Demougeot, Celine;Prigent-Tessier, Anne;Berthelot, Alain
越来越多的证据表明，血管淀粉酶在血管疾病的病理生理学中发挥作用。我们最近报道了在年轻的成年高血压自发性高血压大鼠（SHR）的高β-淀粉酶活性/表达。本研究的目的是描述自发性高血压大鼠中凝血酶途径异常的时间过程，并探讨血流动力学和炎症的作用。实验在5、10、19和26周龄SHR及其同龄对照Wistar京都（WKY）大鼠上进行。在主动脉组织提取物中测定精氨酸酶活性以及精氨酸酶1、精氨酸酶II、内皮型和诱导型NOS的表达。测量血浆中L-精氨酸、NO催化剂和IL-6（炎症标志物）的水平。精氨酸酶活性/表达也在先前用肼苯哒嗪处理的10周龄SHR中测量（20 mg/kg/天，经口，持续5周）。与WKY相比，SHR从高血压前期到高血压的建立阶段表现出高的血管平滑肌酶I和II表达。然而，在高血压前期观察到表达和活性之间的不匹配。精氨酸酶表达与血浆IL-6水平和NOS表达均无相关性。肼苯哒嗪预防高血压显著减弱了β-淀粉酶的上调，并恢复了β-淀粉酶的活性。重要的是，在SHR中，葡萄糖氧化酶活性和血压（BP）相关。总之，我们的研究结果表明，辅酶Ⅱ酶上调之前的血压升高，并确定血压升高作为遗传性高血压辅酶Ⅱ酶失调的一个因素。他们还证明了腺苷酸酶活性与血压之间的密切关系，从而使腺苷酸酶成为抗高血压治疗的有希望的靶点。(c)2006年爱思唯尔公司All rights reserved.
There is growing evidence that vascular arginase plays a role in pathophysiology of vascular diseases. We recently reported high arginase activity/expression in young adult hypertensive spontaneously hypertensive rats (SHR). The aim of the present study was to characterize the time course of arginase pathway abnormalities in SHR and to explore the contributing role of hemodynamics and inflammation. Experiments were conducted on 5, 10, 19 and 26-week-old SHR and their age-matched control Wistar Kyoto (WKY) rats. Arginase activity as well as expression of arginase 1, arginase II, endothelial and inducible NOS were determined in aortic tissue extracts. Levels Of L-arginine, NO catabolites and IL-6 (a marker of inflammation) were measured in plasma. Arginase activity/expression was also measured in 10-week-old SHR previously treated with hydralazine (20 mg/kg/day, per os, for 5 weeks). As compared to WKY, SHR exhibited high vascular arginase I and II expression from prehypertensive to established stages of hypertension. However, a mismatch between expression and activity was observed at the prehypertensive stage. Arginase expression was not related either to plasma IL-6 levels or to expression of NOS. Prevention of hypertension by hydralazine significantly blunted arginase upregulation and restored arginase activity. Importantly, arginase activity and blood pressure (BP) correlated in SHR. In conclusion, our results demonstrate that arginase upregulation precedes blood pressure rising and identify elevated blood pressure as a contributing factor of arginase dysregulation in genetic hypertension. They also demonstrated a close relationship between arginase activity and BP, thus making arginase a promising target for antihypertensive therapy. (c) 2006 Elsevier Inc. All rights reserved.