重复剂量的卡托普利通过调节 TRPV1 受体诱发大鼠气道高反应性。

IF 3.3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Janiana Raíza Jentsch Matias de Oliveira , Mayara Alves Amorim , Vitor Hélio de Souza Oliveira , Daniela de Almeida Cabrini , Michel Fleith Otuki , Claudia Martins Galindo , Bruna Barbosa da Luz , Maria Fernanda de Paula Werner , João Batista Calixto , Eunice André
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引用次数: 0

摘要

虽然 TRPV1 受体在卡托普利治疗后对气道的不良影响中起着至关重要的作用,但目前还没有证据表明它们参与了重复剂量卡托普利的治疗方案。由于卡托普利是一种持续使用的药物,因此比较这两种治疗方案的差异至关重要。因此,本研究采用两种治疗方案,探讨了瞬时受体电位类香草素 1(TRPV1)在卡托普利对大鼠气道影响中的作用。研究人员对单次或多次服用卡托普利的大鼠进行了气道阻力、支气管肺泡灌洗(BAL)、组织学和免疫组化分析。该研究表明,经卡托普利治疗的大鼠对缓激肽和辣椒素的高反应性是急性的。用选择性 B2 拮抗剂 HOE140 治疗可降低缓激肽高反应性,并消除单剂量卡托普利治疗大鼠的辣椒素加重症状。同样,TRPV1 阳性神经元的退化也会降低对缓激肽的高反应性。与药物治疗相比,单剂量卡托普利治疗会增加白细胞在BAL中的浸润,TRPV1阳性神经元变性会减少这种增加。此外,只有重复服用卡托普利的动物才会出现 TRPV1 表达的增加,而 TRPV1 阳性神经元的退化会减弱 TRPV1 的上调。总之,这些数据有力地表明,多剂量卡托普利治疗方案不仅能增强敏感性,还能上调 TRPV1 的表达。因此,以 TRPV1 为靶点可作为减少卡托普利对气道负面影响的一种有前途的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Repeated doses of captopril induce airway hyperresponsiveness by modulating the TRPV1 receptor in rats

Although TRPV1 receptors play an essential role in the adverse effects on the airways following captopril treatment, there is no available evidence of their involvement in treatment regimens involving repeated doses of captopril. Comparing the difference in these two treatment regimens is essential since captopril is a continuous-use medication. Thus, this study explored the role of the transient receptor potential vanilloid 1 (TRPV1) in the effects of captopril on rat airways using two treatment regimens. Airway resistance, bronchoalveolar lavage (BAL), and histological and immunohistochemical analyses were conducted in rats administered with single or repeated doses of captopril. This study showed that the hyperresponsiveness to bradykinin and capsaicin in captopril-treated rats was acute. Treatment with the selective B2 antagonist, HOE140 reduced bradykinin hyperresponsiveness and abolished capsaicin exacerbation in single-dose captopril-treated rats. Likewise, degeneration of TRPV1-positive neurones also reduced hyperresponsiveness to bradykinin. Single-dose captopril treatment increased leukocyte infiltration in the BAL when compared with the vehicle and this increase was reduced by TRPV1-positive neurone degeneration. However, when compared with the vehicle treatment, animals treated with repeated doses of captopril showed an increase in leukocyte influx as early as 1 h after the last captopril treatment, but this effect disappeared after 24 h. Additionally, an increase in TRPV1 expression occurred only in animals who received repeated captopril doses and the degeneration of TRPV1-positive neurones attenuated TRPV1 upregulation. In conclusion, these data strongly indicate that a treatment regimen involving multiple doses of captopril not only enhances sensitisation but also upregulates TRPV1 expression. Consequently, targeting TRPV1 could serve as a promising strategy to reduce the negative impact of captopril on the airways.

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来源期刊
CiteScore
6.20
自引率
0.00%
发文量
41
审稿时长
42 days
期刊介绍: Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews. Research Areas Include: • All major diseases of the lung • Physiology • Pathology • Drug delivery • Metabolism • Pulmonary Toxicology.
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