Homocysteine attenuates hemodynamic responses to nitric oxide in vivo
Homocysteine attenuates hemodynamic responses to nitric oxide in vivo
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DOI：
10.1016/s0021-9150(01)00654-2
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发表时间：
2002-03-01
期刊：
影响因子：
5.3
通讯作者：
Wang, XL
中科院分区：
文献类型：
--
作者：
Fu, WY;Dudman, NPB;Wang, XL
同型半胱氨酸是血管疾病的重要但可改变的危险因素。虽然可能涉及几个病理过程，但同型半胱氨酸可引起显着的内皮损伤和损害血管NO生物活性。在本研究中，我们旨在评估同型半胱氨酸对no介导的体内血流动力学反应的影响。通过对麻醉大鼠持续静脉输注13,1 l -同型半胱氨酸，建立急性高同型半胱氨酸血症模型（血浆同型半胱氨酸为65-276 μ mol/l）。血管扩张剂包括NO供体：s -亚硝基同型半胱氨酸（SNOHcy）、s -亚硝基半胱氨酸（SNOCys）和硝普钠（SNP），内皮NO合成酶（eNOS）激活剂：乙酰胆碱（ACh），钙通道阻滞剂：维拉帕米和硝地平，一次注射给同型半胱氨酸血症大鼠。虽然同型半胱氨酸输注对平均股动脉血压没有影响，但这些血管扩张剂中的每一种都导致血压迅速而显著的剂量依赖性下降。然而，同时输注同型半胱氨酸可减弱NO供体诱导的降血压作用（P < 0.01），而钙通道阻滞剂则无此作用。同型半胱氨酸不仅抑制ACh刺激的内皮源性NO，而且抑制SNOHcy、SNOCys和SNP外源供给NO的生物活性。我们的研究结果表明，同型半胱氨酸可能对一氧化氮的生物产生和生物利用度有影响。高同型半胱氨酸血症严重影响硝酸甘油等常用NO供体的血管舒张作用，而高同型半胱氨酸血症在缺血性心脏病患者中很常见。(C) 2002爱思唯尔科学爱尔兰有限公司版权所有。
Homocysteine is a significant but modifiable risk factor for vascular diseases. While several pathological processes may be involved, homocysteine can cause significant endothelial impairment and compromise vascular NO bioactivity. In the present study, we aimed to assess effects of homocysteine on NO-mediated hemodynamic responses in vivo. We created an acute hyperhomocysteinemia model (plasma homocysteine of 65-276 mumol/l) by continuous venous infusion Of 13,L-homocysteine to anaesthetized Sprague-Dawley rats. Vasodilators including NO donors: S-nitrosohomocysteine (SNOHcy), S-nitrosocysteine (SNOCys) and sodium nitroprusside (SNP), the endothelial NO synthase (eNOS) activator: acetylcholine (ACh), and calcium channel blocker: verapamil and nicardipine, were administered by one bolus injection to the homocysteinemic rats. While homocysteine infusion produced no change in the mean femoral arterial blood pressure, each of these vasodilators led to a rapid and substantial dose-dependent fall in blood pressure. Concurrent homocysteine infusion, however, attenuated the blood pressure lowering effects induced by NO donors (P < 0.01), but not by the calcium channel blockers. Homocysteine inhibited not only the endothelial-derived NO as stimulated by ACh, but also the bioactivity of exogenously supplied NO by SNOHcy, SNOCys and SNP. Our findings indicate that homocysteine may have an effect on NO bioproduction and bioavailability. Vasodilating efficacy of commonly used NO donors such as nitroglycerine may be seriously compromised by hyperhomocysteinemia, which is common among ischemic heart disease patients. (C) 2002 Elsevier science Ireland Ltd. All rights reserved.