糖尿病大鼠心房对 GLP-1 受体激动剂和西他列汀的顺时针反应

IF 2.6 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Esra Akcabag, Zinnet Sevval Aksoyalp, Feride Oner, Zeliha Bayram, Gul Ozbey, Cahit Nacitarhan, Sebahat Ozdem, Arda Tasatargil, Sadi S Ozdem
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引用次数: 0

摘要

摘要:2 型糖尿病(T2DM)会增加罹患心血管疾病的风险。因此,阐明抗糖尿病药物对心血管的影响至关重要。基于胰岛素的疗法越来越多地被用于 T2DM 的单药或联合治疗。我们旨在研究胰高血糖素样肽-1受体激动剂(GLP-1 RAs)和西他列汀对糖尿病大鼠离体心房跳动率的影响。研究人员测定了对照组大鼠和糖尿病大鼠离体心房对 GLP-1 RAs 和西他列汀单药治疗以及与二甲双胍、吡格列酮和格列美脲联合治疗的促时反应。GLP-1 (7-36)、GLP-1 (9-36) 和 Exendin-4 (1-39) 均能提高对照组和糖尿病大鼠心房的跳动率。然而,西他列汀只增加了糖尿病组的跳动频率。Exendin (9-39)、L-NAME 和吲哚美辛能阻止对 GLP-1 RAs 的反应,但不能阻止对西他列汀的反应。格列本脲、4-氨基吡啶、阿帕明、胭脂虫毒素、超氧化物歧化酶和过氧化氢酶孵育不会改变对 GLP-1 RAs 和西他列汀的反应。GLP-1 RAs 通过 GLP-1 受体、一氧化氮和环氧化酶途径增加离体大鼠心房的跳动率,但不通过钾通道和活性氧自由基。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chronotropic Responses to GLP-1 Receptor Agonists and Sitagliptin in Atria From Diabetic Rats.

Abstract: Type 2 diabetes mellitus increases the risk of cardiovascular diseases. Therefore, elucidation of the cardiovascular effects of antidiabetics is crucial. Incretin-based therapies are increasingly used for type 2 diabetes mellitus treatment as monotherapy and in combination. We aimed to study the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sitagliptin on beating rates in isolated atria from diabetic rats. The chronotropic responses to GLP-1 RAs and sitagliptin as monotherapy and in combinations with metformin, pioglitazone, and glimepiride in isolated atria from control and diabetic rats were determined. GLP-1 (7-36), GLP-1 (9-36), and exendin-4 (1-39) produced increases in beating rates in both control and diabetic rat atria. However, sitagliptin increased the beating frequency only in the diabetic group. Exendin (9-39), nitro- l -arginine methyl ester hydrochloride, and indomethacin blocked responses to GLP-1 RAs but not the response to sitagliptin. Glibenclamide, 4-aminopyridine, apamin, charybdotoxin, superoxide dismutase, and catalase incubations did not change responses to GLP-1 RAs and sitagliptin. GLP-1 RAs increase beating rates in isolated rat atrium through GLP-1 receptor, nitric oxide, and cyclooxygenase pathways but not potassium channels and reactive oxygen radicals.

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来源期刊
CiteScore
5.10
自引率
3.30%
发文量
367
审稿时长
1 months
期刊介绍: Journal of Cardiovascular Pharmacology is a peer reviewed, multidisciplinary journal that publishes original articles and pertinent review articles on basic and clinical aspects of cardiovascular pharmacology. The Journal encourages submission in all aspects of cardiovascular pharmacology/medicine including, but not limited to: stroke, kidney disease, lipid disorders, diabetes, systemic and pulmonary hypertension, cancer angiogenesis, neural and hormonal control of the circulation, sepsis, neurodegenerative diseases with a vascular component, cardiac and vascular remodeling, heart failure, angina, anticoagulants/antiplatelet agents, drugs/agents that affect vascular smooth muscle, and arrhythmias. Appropriate subjects include new drug development and evaluation, physiological and pharmacological bases of drug action, metabolism, drug interactions and side effects, application of drugs to gain novel insights into physiology or pathological conditions, clinical results with new and established agents, and novel methods. The focus is on pharmacology in its broadest applications, incorporating not only traditional approaches, but new approaches to the development of pharmacological agents and the prevention and treatment of cardiovascular diseases. Please note that JCVP does not publish work based on biological extracts of mixed and uncertain chemical composition or unknown concentration.
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