Arterial 5-hydroxytryptamine transporter function is impaired in deoxycorticosterone acetate and Nomega-nitro-L-arginine but not spontaneously hypertensive rats.
Arterial 5-hydroxytryptamine transporter function is impaired in deoxycorticosterone acetate and Nomega-nitro-L-arginine but not spontaneously hypertensive rats.
复制标题
醋酸脱氧皮质酮和 Nomega-硝基-L-精氨酸的动脉 5-羟色胺转运蛋白功能受损，但自发性高血压大鼠并未受损。
DOI：
10.1161/01.hyp.0000225754.15146.dd
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Watts,StephanieW
中科院分区：
文献类型：
--
作者：
Ni,Wei;Lookingland,Keith;Watts,StephanieW
我们报道了5-羟色胺（HT）转运体（5-HTT）蛋白在脱氧皮质酮醋酸盐（DOCA）高血压大鼠外周动脉的上调。我们假设，上调5-HTT可能普遍升高，在高血压模型，因此，较高的基础浓度的5-HT，5-HT代谢产物5-羟基吲哚乙酸，和增加5-HT摄取将发生在外周动脉高血压大鼠与血压正常大鼠相比。本研究中，我们检查了3种高血压模型：DOCA-盐大鼠、Nω-硝基-L-精氨酸（LNNA）大鼠和自发性高血压大鼠（SHR）（收缩压[mm Hg]：DOCA（D）=197±6，SHAM（D）=112±4，LNNA（L）=228±9，SHAM（L）=128±2，SHR=172±7，Wistar-Kyoto [WKY]= 121±3）。高压液相色谱法测量显示，较低的基础5-HT浓度在主动脉DOCA盐和LNNA大鼠与他们的SHAM大鼠相比，但在SHR与WKY相比。在所有的5-HT-摄取研究中，我们使用了从单胺氧化酶-A抑制剂帕吉林处理的大鼠中分离的动脉，以最大限度地减少5-HT代谢。外源性5-HT可被主动脉摄取，5-HT抑制剂氟西汀（1 μmol/L）或氟伏沙明（1 μmol/L）可抑制主动脉摄取。DOCA-盐和LNNA大鼠主动脉5-HT总摄取和5-HT依赖性主动摄取均低于SHAM大鼠，但SHR与WKY相比未观察到这一点。Western分析显示，WKY和SHR主动脉中5-HTT的表达相似，而DOCA盐和LNNA高血压大鼠主动脉中5-HTT的表达上调。我们的研究表明，在DOCA盐和LNNA高血压大鼠中，5-HTT功能受损引起的肾上腺素能系统的改变可能在血压调节中起作用。
We reported upregulation of the 5-hydroxytryptamine (HT) transporter (5-HTT) protein in peripheral arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We hypothesized that upregulated 5-HTT may be generally elevated in hypertensive models and, as a consequence, a higher basal concentration of 5-HT, the 5-HT metabolite 5-hydroxyindoleacetic acid, and an increased 5-HT uptake would occur in peripheral arteries of hypertensive rats compared with normotensive rats. We examined 3 hypertension models: DOCA-salt rats, Nω-nitro-l-arginine (LNNA) rats, and spontaneously hypertensive rats (SHRs) in our study (systolic blood pressure [mm Hg]: DOCA (D)=197±6, SHAM(D)=112±4, LNNA (L)=228±9, SHAM(L)=128±2, SHR=172±7, and Wistar-Kyoto [WKY]= 121±3). High-pressure liquid chromatography measurements showed lower basal 5-HT concentrations in aorta from DOCA-salt and LNNA rats compared with their SHAM rats but not in SHR compared with WKY. In all of the 5-HT-uptake studies, we used arteries isolated from rats treated with the monoamine oxidase-A inhibitor pargyline to minimize 5-HT metabolism. Exogenous 5-HT was taken up by aorta, and this was inhibited by the 5-HTT inhibitor fluoxetine (1 μmol/L) or fluvoxamine (1 μmol/L). Total 5-HT uptake and 5-HTT–dependent active 5-HT uptake were decreased in aorta from DOCA-salt and LNNA rats compared with SHAM rats, but this was not observed in SHRs compared with WKYs. Western analysis revealed similar expression of 5-HTT in aorta from WKYs and SHRs as opposed to an upregulated 5-HTT in aorta from DOCA-salt and LNNA-hypertensive rats. Our study suggested that an altered serotonergic system by impaired 5-HTT function might play a role in blood pressure regulation in DOCA-salt and LNNA-hypertensive rats.