Pyridoxal-5′-phosphate: A cost-effective treatment candidate for hypertensive patients?

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine Pub Date : 2024-10-10 DOI:10.1111/joim.20015

Michaela Lellig, Mariano Rodríguez, Rodrigo López-Baltanás, Juliane Hermann, Julia Wollenhaupt, Heidi Noels, Walter Zidek, Martin Tepel, Felix Mahfoud, Joachim Jankowski, Juan R. Muñoz-Castañeda, Vera Jankowski

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Abstract

Objectives

Because angiotensin (Ang) II is an essential vasoconstrictive peptide, we analyzed the impact of its post-translational modification to pyruvamide–Ang II (Ang P) by pyridoxal-5′-phosphate (PLP) on blood pressure. PLP is a less expensive vitamin B₆ derivative and, therefore, could be a cost-effective drug against hypertension.

Methods

Effect of Ang P on calcium ion entry into vascular smooth muscle cells (VSMCs) was analyzed. Binding affinity of Ang P to angiotensin II type 1 receptor (AT₁R) was measured. Vasoconstrictive effect of Ang P was investigated using the bioassay of isolated perfused rat kidneys. Spontaneously hypertensive rats (SHR) were administered PLP. Additionally, Wistar Kyoto rats (WKY) received Ang II and PLP. Blood pressure was measured time-dependently.

Results

Ang II, incubated with PLP, was post-translationally modified to Ang P. Calcium ion entry in VSMCs was significantly lower with Ang P compared to Ang II. Binding affinity of Ang P to AT₁R was lower compared to Ang II. Perfusion pressure of isolated perfused rat kidneys increased less by Ang P than by Ang II. Blood pressure of SHR treated with PLP decreased significantly. Blood pressure of WKY rats treated with Ang II was increased to hypertensive values, whereas blood pressure of WKY rats cotreated with Ang II and PLP was not.

Conclusion

PLP induces a post-translational modification of Ang II decreasing blood pressure in rats. Assuming that increased PLP intake in the form of vitamin B₆ might reduce blood pressure in hypertensive patients, PLP might be a cost-effective drug against hypertension.

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5'-磷酸吡哆醛：高血压患者的经济有效治疗方法？

研究目的由于血管紧张素（Ang）II是一种重要的血管收缩肽，我们分析了5'-磷酸吡哆醛（PLP）将其翻译后修饰为丙酮酰胺-Ang II（Ang P）对血压的影响。PLP是一种价格较低的维生素B6衍生物，因此可以成为一种经济有效的高血压药物：方法：分析 Ang P 对钙离子进入血管平滑肌细胞（VSMCs）的影响。测量了 Ang P 与血管紧张素 II 1 型受体（AT1R）的结合亲和力。使用离体灌注大鼠肾脏的生物测定法研究了 Ang P 的血管收缩效应。给自发性高血压大鼠（SHR）注射 PLP。此外，Wistar Kyoto 大鼠（WKY）接受 Ang II 和 PLP。血压测量与时间有关：与 Ang II 相比，Ang P 在血管内皮细胞中的钙离子进入量明显降低。Ang P 与 AT1R 的结合亲和力低于 Ang II。Ang P 对离体灌注大鼠肾脏灌注压的增加低于 Ang II。用 PLP 治疗 SHR 的血压明显下降。用 Ang II 治疗的 WKY 大鼠的血压升高至高血压值，而 Ang II 和 PLP 联合治疗的 WKY 大鼠的血压则没有升高：结论：PLP 可诱导 Ang II 翻译后修饰，降低大鼠血压。假设增加维生素 B6 形式的 PLP 摄入量可降低高血压患者的血压，那么 PLP 可能是一种经济有效的高血压防治药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Internal Medicine 医学-医学：内科

CiteScore

22.00

自引率

0.90%

发文量

176

审稿时长

4-8 weeks

期刊介绍： JIM – The Journal of Internal Medicine, in continuous publication since 1863, is an international, peer-reviewed scientific journal. It publishes original work in clinical science, spanning from bench to bedside, encompassing a wide range of internal medicine and its subspecialties. JIM showcases original articles, reviews, brief reports, and research letters in the field of internal medicine.