Sarah Pribil Pardun , Spencer Duff , Ian Papenfus , Will Bruening , Yulong Li , Gurudutt Pendyala , Lie Gao
{"title":"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","authors":"Sarah Pribil Pardun , Spencer Duff , Ian Papenfus , Will Bruening , Yulong Li , Gurudutt Pendyala , Lie Gao","doi":"10.1016/j.ejphar.2025.177828","DOIUrl":null,"url":null,"abstract":"<div><div>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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup> 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.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177828"},"PeriodicalIF":4.7000,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Combined effects of gabapentin with verapamil and metoprolol on cardiovascular function of anesthetized male rats\",\"authors\":\"Sarah Pribil Pardun , Spencer Duff , Ian Papenfus , Will Bruening , Yulong Li , Gurudutt Pendyala , Lie Gao\",\"doi\":\"10.1016/j.ejphar.2025.177828\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup> 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.</div></div>\",\"PeriodicalId\":12004,\"journal\":{\"name\":\"European journal of pharmacology\",\"volume\":\"1002 \",\"pages\":\"Article 177828\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-06-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European journal of pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0014299925005825\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014299925005825","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.