Souza-Silva Igor Maciel, de Paula Cristiane Amorim, Bolais-Ramos Lucas, Santos Anderson Kenedy, da Silva Filipe Alex, de Oliveira Vívian Louise Soares, da Rocha Isabella Domingos, Antunes Maísa Mota, Cordeiro Lídia Pereira Barbosa, Teixeira Vanessa Pereira, Scalzo Júnior Sérgio Ricardo Aluotto, Raabe Adriana Campezatto, Guimaraes Pedro Pires Goulart, Amaral Flávio Almeida, Resende Jarbas Magalhães, Fontes Marco Antônio Peliky, Menezes Gustavo Batista, Guatimosim Silvia, Santos Robson Augusto Souza, Verano-Braga Thiago
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Br J Pharmacol. 2022 Jun;179(12):3061-3077. doi: 10.1111/bph.15790. Epub 2022 Feb 9.
Bradykinin (BK-(1-9)) is an endogenous nonapeptide involved in multiple physiological and pathological processes. Peptide fragments of bradykinin are believed to be biologically inactive. We have now tested the two major peptide fragments of bradykinin in human and animals.
BK peptides were quantified by MS in male rats. NO release was quantified from human, mouse and rat cells loaded with DAF-FM. Rat aortic rings were used to measure vascular reactivity. Changes in BP and HR were measured in conscious male rats. To evaluate pro-inflammatory effects both vascular permeability and nociception were measured in adult mice.
BK-(1-7) and BK-(1-5) are produced in vivo from BK-(1-9). Both peptides induced NO production in all cell types tested. However, unlike BK-(1-9), NO production elicited by BK-(1-7) or BK-(1-5) was not inhibited by B or B receptor antagonists. BK-(1-7) and BK-(1-5) induced concentration-dependent vasorelaxation of aortic rings, without involvement of B or B receptors. Intravenous or intra-arterial administration of BK-(1-7) or BK-(1-5) induced similar hypotensive response in vivo. Nociceptive responses of BK-(1-7) and BK-(1-5) were reduced compared to BK-(1-9), and no increase in vascular permeability was observed for BK-(1-9) fragments.
BK-(1-7) and BK-(1-5) are endogenous peptides present in plasma. BK-related peptide fragments show biological activity, not mediated by B or B receptors. These BK fragments could constitute new, active components of the kallikrein-kinin system.
缓激肽（BK-(1-9)）是一种内源性九肽，参与多种生理和病理过程。缓激肽的肽片段被认为无生物活性。我们现已在人和动物中测试了缓激肽的两种主要肽片段。
通过质谱法对雄性大鼠体内的BK肽进行定量。用DAF-FM加载的人、小鼠和大鼠细胞中NO释放量进行定量。用大鼠主动脉环测量血管反应性。在清醒雄性大鼠中测量血压和心率变化。为评估促炎作用，在成年小鼠中测量血管通透性和痛觉感受。
BK-(1-7)和BK-(1-5)在体内由BK-(1-9)产生。两种肽在所有测试细胞类型中均诱导NO生成。然而，与BK-(1-9)不同，BK-(1-7)或BK-(1-5)引发的NO生成不受B或B受体拮抗剂抑制。BK-(1-7)和BK-(1-5)诱导主动脉环浓度依赖性血管舒张，不涉及B或B受体。静脉或动脉内给予BK-(1-7)或BK-(1-5)在体内诱导相似的降压反应。与BK-(1-9)相比，BK-(1-7)和BK-(1-5)的痛觉反应降低，且未观察到BK-(1-9)片段导致血管通透性增加。
BK-(1-7)和BK-(1-5)是血浆中存在的内源性肽。BK相关肽片段显示出生物活性，并非由B或B受体介导。这些BK片段可能构成激肽释放酶-激肽系统的新的活性成分。
