Interaction of Angiotensin-(1−7) with kinins in the kidney circulation: Role of B1 receptors

IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Peptides Pub Date : 2024-05-29 DOI:10.1016/j.peptides.2024.171246
Elizabeth Pereira Mendes , Danielle Ianzer , Diogo Barros Peruchetti , Robson Augusto Souza Santos , Maria Aparecida Ribeiro Vieira
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Abstract

Changes in renal hemodynamics impact renal function during physiological and pathological conditions. In this context, renal vascular resistance (RVR) is regulated by components of the Renin-Angiotensin System (RAS) and the Kallikrein-Kinin System (KKS). However, the interaction between these vasoactive peptides on RVR is still poorly understood. Here, we studied the crosstalk between angiotensin-(1−7) and kinins on RVR. The right kidneys of Wistar rats were isolated and perfused in a closed-circuit system. The perfusion pressure and renal perfusate flow were continuously monitored. Ang-(1−7) (1.0–25.0 nM) caused a sustained, dose-dependent reduction of relative RVR (rRVR). This phenomenon was sensitive to 10 nM A-779, a specific Mas receptor (MasR) antagonist. Bradykinin (BK) promoted a sustained and transient reduction in rRVR at 1.25 nM and 125 nM, respectively. The transient effect was abolished by 4 μM des-Arg9-Leu8-bradykinin (DALBK), a specific kinin B1 receptor (B1R) antagonist. Accordingly, des-Arg9-bradykinin (DABK) 1 μM (a B1R agonist) increased rRVR. Interestingly, pre-perfusion of Ang-(1−7) changed the sustained reduction of rRVR triggered by 1.25 nM BK into a transient effect. On the other hand, pre-perfusion of Ang-(1−7) primed and potentiated the DABK response, this mechanism being sensitive to A-779 and DALBK. Binding studies performed with CHO cells stably transfected with MasR, B1R, and kinin B2 receptor (B2R) showed no direct interaction between Ang-(1−7) with B1R or B2R. In conclusion, our findings suggest that Ang-(1−7) differentially modulates kinin's effect on RVR in isolated rat kidneys. These results help to expand the current knowledge regarding the crosstalk between the RAS and KKS complex network in RVR.

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肾循环中血管紧张素-(1-7)与激肽的σ相互作用:B1 受体的作用。
在生理和病理条件下,肾血流动力学的变化会影响肾功能。在这种情况下,肾血管阻力(RVR)受肾素-血管紧张素系统(RAS)和Kallikrein-激肽系统(KKS)成分的调节。然而,人们对这些血管活性肽与 RVR 之间的相互作用仍然知之甚少。在此,我们研究了血管紧张素-(1-7)和激肽对 RVR 的相互影响。我们分离了 Wistar 大鼠的右肾,并在闭路系统中进行灌注。对灌注压力和肾灌注液流量进行连续监测。Ang-(1-7)(1.0-25.0nM)导致相对 RVR(rRVR)持续、剂量依赖性降低。这种现象对 10nM A-779 很敏感,A-779 是一种特异性 Mas 受体(MasR)拮抗剂。缓激肽(BK)分别在 1.25nM 和 125nM 时促进 rRVR 的持续和短暂降低。4μM des-Arg9-Leu8-缓激肽(DALBK)(一种特异性激肽 B1 受体(B1R)拮抗剂)可消除瞬时效应。相应地,1μM des-Arg9-缓激肽(DABK)(一种 B1R 激动剂)可增加 rRVR。有趣的是,预灌注 Ang-(1-7) 使 1.25nM BK 引发的 rRVR 持续降低转变为短暂效应。另一方面,Ang-(1-7)的预灌注启动并增强了 DABK 反应,这种机制对 A-779 和 DALBK 敏感。用稳定转染 MasR、B1R 和缓激肽 B2 受体的 CHO 细胞进行的结合研究表明,Ang-(1-7)与 B1R 或 B2R 之间没有直接相互作用。总之,我们的研究结果表明,在离体大鼠肾脏中,Ang-(1-7)可不同程度地调节激肽对 RVR 的影响。这些结果有助于扩展目前有关 RAS 和 KKS 复合物网络在 RVR 中相互影响的知识。
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来源期刊
Peptides
Peptides 医学-生化与分子生物学
CiteScore
6.40
自引率
6.70%
发文量
130
审稿时长
28 days
期刊介绍: Peptides is an international journal presenting original contributions on the biochemistry, physiology and pharmacology of biological active peptides, as well as their functions that relate to gastroenterology, endocrinology, and behavioral effects. Peptides emphasizes all aspects of high profile peptide research in mammals and non-mammalian vertebrates. Special consideration can be given to plants and invertebrates. Submission of articles with clinical relevance is particularly encouraged.
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