一氧化氮与细胞色素 P-450 系统在大鼠血压和肾功能中的相互作用：钠摄入量的依赖性。

Interaction of nitric oxide and the cytochrome P-450 system on blood pressure and renal function in the rat: dependence on sodium intake.

机构信息

Laboratory of Renal and Body Fluid Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

出版信息

Acta Physiol (Oxf). 2011 Apr;201(4):493-502. doi: 10.1111/j.1748-1716.2010.02222.x. Epub 2010 Dec 8.

DOI:10.1111/j.1748-1716.2010.02222.x

PMID:21073660

Abstract

AIM

Interaction was examined of nitric oxide (NO) and cytochrome P-450 (CYP-450)-dependent arachidonic acid derivatives, 20-HETE and EETs, in control of arterial pressure (MABP) and renal function. Modification of this interaction by changing sodium intake was also studied.

METHODS

On low, standard or high Na diet (LS, STD and HS rats respectively) effects of sequential blockade of NO synthases (NOS) and CYP-450 enzyme activity on MABP, renal blood flow (RBF, Transonic probe), renal medullary perfusion (MBF, laser-Doppler technique), medullary tissue NO (selective electrode) and renal excretion were examined in anaesthetized rats. All NOS were blocked with N(ϖ) -nitro-l-arginine methyl ester (l-NAME), the neuronal NOS with S-methyl-l-thiocitrulline (SMTC), and CYP-450 with 1-aminobenzotriazole (ABT).

RESULTS

In each diet group the baseline MABP was highest in rats pre-treated with l-NAME. CYP-450 inhibition significantly decreased MABP only in LS (-9%) and HS rats (-22%) pre-treated with l-NAME. This MABP decrease correlated directly with the dietary sodium content (r = 0.644, P < 0.001). CYP-450 inhibition decreased RBF in LS and HS rats (not in HS pre-treated with l-NAME). Acute exclusion of CYP-450 significantly increased MBF only in STD, SMTC pre-treated rats; in HS group it significantly increased medullary tissue NO by about 1.0 nA. The post-ABT changes in renal excretion occurred in LS and HS rats, irrespective of the status of NO synthesis.

CONCLUSIONS

Both NO- and CYP-450-dependent agents contribute to blood pressure and kidney function control, however, the role of 20-HETE and EETs becomes crucial only under conditions of high sodium intake or after NOS inhibition.

摘要

目的

研究一氧化氮（NO）和细胞色素 P-450（CYP-450）依赖性花生四烯酸衍生物 20-HETE 和 EETs 在控制动脉血压（MABP）和肾功能方面的相互作用。还研究了通过改变钠摄入量来改变这种相互作用的情况。

方法

在低、标准或高钠饮食（LS、STD 和 HS 大鼠）下，在麻醉大鼠中，连续阻断一氧化氮合酶（NOS）和 CYP-450 酶活性对 MABP、肾血流量（RBF，Transonic 探头）、肾髓质灌注（MBF，激光多普勒技术）、髓质组织 NO（选择性电极）和肾排泄的影响。所有 NOS 均用 N（ω）-硝基-L-精氨酸甲酯（l-NAME）阻断，神经元 NOS 用 S-甲基-L-硫代瓜氨酸（SMTC）阻断，CYP-450 用 1-氨基苯并三唑（ABT）阻断。

结果

在每个饮食组中，用 l-NAME 预处理的大鼠基础 MABP 最高。CYP-450 抑制仅在 LS（-9%）和 HS 大鼠（-22%）用 l-NAME 预处理时显著降低 MABP。这种 MABP 下降与饮食中钠含量直接相关（r = 0.644，P < 0.001）。CYP-450 抑制降低了 LS 和 HS 大鼠的 RBF（HS 用 l-NAME 预处理的大鼠则没有）。急性排除 CYP-450 仅在 STD、SMTC 预处理的大鼠中显著增加 MBF；在 HS 组中，它显著增加了约 1.0 nA 的髓质组织 NO。ABT 后的肾排泄变化发生在 LS 和 HS 大鼠中，与 NO 合成状态无关。