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麻醉大鼠对多巴胺前体输注的肾脏反应。

Renal response to infusion of dopamine precursors in anaesthetized rats.

作者信息

Mühlbauer B, Gleiter C H, Gies C, Luippold G, Löschmann P A

机构信息

Pharmakologisches Institut der Universität Tübingen, Germany.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1997 Dec;356(6):838-45. doi: 10.1007/pl00005125.

Abstract

In the present study the renal response to intravenous infusion of the catecholamine precursors L-dihydroxyphenylalanine (L-DOPA) or L-tyrosine was investigated in thiopentone sodium-anaesthetized Sprague-Dawley rats. Glomerular filtration rate (GFR) was assessed by renal clearance of inulin, urinary concentration of dopamine (U(DA)V) by HPLC and sodium excretion (U(Na)V) by flame photometry. We found that basal U(DA)V was 6.5 +/- 0.5 pmol/min per 100 g body weight (mean +/- SEM). Intravenous infusion of L-tyrosine at 0. 1-3.0 micromol/min dose dependently enhanced U(DA)V (17 +/- 3 to 144 +/- 14 pmol/min respectively) with higher doses of L-tyrosine resulting in no further increase in U(DA)V. Compared with L-tyrosine administration significantly lower doses of L-DOPA (0.07 to 35 nmol/min) caused increases in U(DA)V which were orders of magnitude higher (18 +/- 1 to 7800 +/- 470 pmol/min, respectively) and did not show saturation characteristics. GFR did not change in response to L-tyrosine or L-DOPA infusion. No variations in urinary flow rate or in U(Na)V could be observed which were significantly correlated to changes in U(DA)V. In contrast, intravenous infusion of dopamine at a dose of 6 nmol/min significantly increased GFR by 35 +/- 6.2% and urinary flow rate by over 2-fold. Immunohistochemistry with light microscopy revealed no tyrosine hydroxylase in the kidney. Therefore, dopamine synthesis in the tubular cells mainly depends on the renal supply of L-DOPA. The unchanged GFR and U(Na)V in spite of large variations of U(DA)V argue against the hypothesis that intratubular dopamine plays a functional role in the regulation of hemodynamics or sodium transport in the kidney. Renal dopamine excretion may rather represent an effective pathway for the elimination of catecholamine precursors from the plasma.

摘要

在本研究中,我们在硫喷妥钠麻醉的Sprague-Dawley大鼠中研究了肾脏对静脉输注儿茶酚胺前体L-二羟基苯丙氨酸(L-DOPA)或L-酪氨酸的反应。通过菊粉肾清除率评估肾小球滤过率(GFR),通过高效液相色谱法测定尿多巴胺浓度(U(DA)V),通过火焰光度法测定尿钠排泄量(U(Na)V)。我们发现基础U(DA)V为每100克体重6.5±0.5 pmol/分钟(平均值±标准误)。以0.1 - 3.0微摩尔/分钟的剂量静脉输注L-酪氨酸可剂量依赖性地提高U(DA)V(分别从17±3至144±14 pmol/分钟),更高剂量的L-酪氨酸不会导致U(DA)V进一步增加。与L-酪氨酸给药相比,显著更低剂量的L-DOPA(0.07至35纳摩尔/分钟)可使U(DA)V增加,增加幅度高出几个数量级(分别为18±1至7800±470 pmol/分钟),且未表现出饱和特性。GFR对L-酪氨酸或L-DOPA输注无反应。未观察到尿流率或U(Na)V的变化与U(DA)V的变化有显著相关性。相比之下,以6纳摩尔/分钟的剂量静脉输注多巴胺可使GFR显著增加35±6.2%,尿流率增加超过2倍。光镜免疫组织化学显示肾脏中无酪氨酸羟化酶。因此,肾小管细胞中的多巴胺合成主要依赖于肾脏对L-DOPA的供应。尽管U(DA)V有很大变化,但GFR和U(Na)V未改变,这与肾小管内多巴胺在肾脏血流动力学或钠转运调节中起功能作用的假设相悖。肾脏多巴胺排泄可能更代表从血浆中清除儿茶酚胺前体的有效途径。

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