加巴喷丁联合维拉帕米、美托洛尔对麻醉雄性大鼠心血管功能的影响

IF 4.7 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Sarah Pribil Pardun , Spencer Duff , Ian Papenfus , Will Bruening , Yulong Li , Gurudutt Pendyala , Lie Gao
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引用次数: 0

摘要

高血浆浓度的加巴喷丁(GBP)会对心血管功能产生负面影响,导致大鼠心动过缓、低血压和左心室(LV)功能受损。本研究考察了GBP联合Verapamil (Ver)或Metoprolol (Met)对麻醉雄性大鼠心血管功能的影响及其对培养H9c2细胞中Ca2+电流和钙调素(CaM)蛋白表达的影响。将22只雄性Sprague Dawley大鼠分为4组:Saline + Ver、GBP + Ver、Saline + Met和GBP + Met。在异氟醚麻醉下,监测大鼠心电图,评估左室血流动力学和血压(BP)。静脉滴注GBP (50 mg/kg),随后滴注Ver (0.05-0.4 mg/kg)或Met (0.5 mg/kg)。在第一个实验中,Ver诱导生理盐水对照组和gbp处理组的血压、心率(HR)和最大dP/dt呈剂量依赖性降低,同时增加最小dP/dt,后一组效果更大。在第二个实验中,与基线相比,GBP显著降低了BP、HR和最大dP/dt,同时增加了最小dP/dt。与单独使用Met相比,Met进一步加剧了这些影响,导致BP、HR和最大dP/dt的更大降低,以及最小dP/dt的增加。此外,体外实验表明,GBP降低Ca2+电流,下调CaM蛋白。这些发现表明,在高血浆浓度下,GBP增强了Ver和Met的负性变时性、负性肌力和降压作用,进一步强调了需要进行额外的临床前和临床研究,以表征GBP与钙通道阻滞剂或β -1阻滞剂之间潜在的药物相互作用,特别是在心血管疾病患者中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Combined effects of gabapentin with verapamil and metoprolol on cardiovascular function of anesthetized male rats

Combined effects of gabapentin with verapamil and metoprolol on cardiovascular function of anesthetized male rats
Gabapentin (GBP), at high plasma concentrations, negatively impacts cardiovascular function, causing bradycardia, hypotension, and impaired left ventricular (LV) function in rats. This study examines the combined effects of GBP with Verapamil (Ver) or Metoprolol (Met) on cardiovascular function in anesthetized male rats and its impact on Ca2+ current and calmodulin (CaM) protein expression in cultured H9c2 cells. Twenty-two male Sprague Dawley rats were assigned to four groups: Saline + Ver, GBP + Ver, Saline + Met, and GBP + Met. Under isoflurane anesthesia, rats underwent ECG monitoring and LV hemodynamic and blood pressure (BP) assessment. GBP (50 mg/kg) was administered intravenously, followed by Ver (0.05–0.4 mg/kg) or Met (0.5 mg/kg). In the first experiment, Ver induced a dose-dependent reduction in BP, heart rate (HR), and maximal dP/dt, while increasing minimal dP/dt, in both saline control and GBP-treated groups with the latter group showing greater effects. In the second experiment, GBP significantly reduced BP, HR, and maximal dP/dt while increasing minimal dP/dt compared to baseline. These effects were further exacerbated by Met, leading to greater reductions in BP, HR, and maximal dP/dt, and increases in minimal dP/dt compared to Met alone. In addition, in vitro experiments demonstrated that GBP reduced Ca2+ current and downregulated CaM protein. These findings suggest that, at high plasma concentrations, GBP enhances the negative chronotropic, negative inotropic, and hypotensive effects of both Ver and Met, further highlighting the need for additional preclinical and clinical studies to characterize the potential drug interactions between GBP and calcium channel blockers or beta-1 blockers, particularly in patients with cardiovascular disease.
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来源期刊
CiteScore
9.00
自引率
0.00%
发文量
572
审稿时长
34 days
期刊介绍: The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.
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