Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats
Gabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant for the treatment of partial seizures and neuropathic pain. Whereas a majority of the side effects are associated with the nervous system, emerging evidence suggests there is a high risk of heart diseases in patients taking GB...
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MDPI AG
2023-11-01
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| author | Ved Vasishtha Pendyala Sarah Pribil Victoria Schaal Kanika Sharma Sankarasubramanian Jagadesan Li Yu Vikas Kumar Chittibabu Guda Lie Gao |
| author_facet | Ved Vasishtha Pendyala Sarah Pribil Victoria Schaal Kanika Sharma Sankarasubramanian Jagadesan Li Yu Vikas Kumar Chittibabu Guda Lie Gao |
| author_sort | Ved Vasishtha Pendyala |
| collection | DOAJ |
| description | Gabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant for the treatment of partial seizures and neuropathic pain. Whereas a majority of the side effects are associated with the nervous system, emerging evidence suggests there is a high risk of heart diseases in patients taking GBP. In the present study, we first used a preclinical model of rats to investigate, firstly, the acute cardiovascular responses to GBP (bolus <i>i.v.</i> injection, 50 mg/kg) and secondly the effects of chronic GBP treatment (<i>i.p.</i> 100 mg/kg/day × 7 days) on cardiovascular function and the myocardial proteome. Under isoflurane anesthesia, rat blood pressure (BP), heart rate (HR), and left ventricular (LV) hemodynamics were measured using Millar pressure transducers. The LV myocardium and brain cortex were analyzed by proteomics, bioinformatics, and western blot to explore the molecular mechanisms underlying GBP-induced cardiac dysfunction. In the first experiment, we found that <i>i.v.</i> GBP significantly decreased BP, HR, maximal LV pressure, and maximal and minimal dP/dt, whereas it increased IRP-AdP/dt, Tau, systolic, diastolic, and cycle durations (* <i>p</i> < 0.05 and ** <i>p</i> < 0.01 vs. baseline; <i>n</i> = 4). In the second experiment, we found that chronic GBP treatment resulted in hypotension, bradycardia, and LV systolic dysfunction, with no change in plasma norepinephrine. In the myocardium, we identified 109 differentially expressed proteins involved in calcium pathways, cholesterol metabolism, and galactose metabolism. Notably, we found that calmodulin, a key protein of intracellular calcium signaling, was significantly upregulated by GBP in the heart but not in the brain. In summary, we found that acute and chronic GBP treatments suppressed cardiovascular function in rats, which is attributed to abnormal calcium signaling in cardiomyocytes. These data reveal a novel side effect of GBP independent of the nervous system, providing important translational evidence to suggest that GBP can evoke adverse cardiovascular events by depression of myocardial function. |
| first_indexed | 2024-03-09T01:53:49Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T01:53:49Z |
| publishDate | 2023-11-01 |
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| spelling | doaj.art-62e3a251a8ae4cec942e62c4ab55aec02023-12-08T15:13:06ZengMDPI AGCells2073-44092023-11-011223270510.3390/cells12232705Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of RatsVed Vasishtha Pendyala0Sarah Pribil1Victoria Schaal2Kanika Sharma3Sankarasubramanian Jagadesan4Li Yu5Vikas Kumar6Chittibabu Guda7Lie Gao8Department of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USADepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USADepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USAMass Spectrometry and Proteomics Core Facility, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USADepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USADepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USAMass Spectrometry and Proteomics Core Facility, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USADepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USADepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USAGabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant for the treatment of partial seizures and neuropathic pain. Whereas a majority of the side effects are associated with the nervous system, emerging evidence suggests there is a high risk of heart diseases in patients taking GBP. In the present study, we first used a preclinical model of rats to investigate, firstly, the acute cardiovascular responses to GBP (bolus <i>i.v.</i> injection, 50 mg/kg) and secondly the effects of chronic GBP treatment (<i>i.p.</i> 100 mg/kg/day × 7 days) on cardiovascular function and the myocardial proteome. Under isoflurane anesthesia, rat blood pressure (BP), heart rate (HR), and left ventricular (LV) hemodynamics were measured using Millar pressure transducers. The LV myocardium and brain cortex were analyzed by proteomics, bioinformatics, and western blot to explore the molecular mechanisms underlying GBP-induced cardiac dysfunction. In the first experiment, we found that <i>i.v.</i> GBP significantly decreased BP, HR, maximal LV pressure, and maximal and minimal dP/dt, whereas it increased IRP-AdP/dt, Tau, systolic, diastolic, and cycle durations (* <i>p</i> < 0.05 and ** <i>p</i> < 0.01 vs. baseline; <i>n</i> = 4). In the second experiment, we found that chronic GBP treatment resulted in hypotension, bradycardia, and LV systolic dysfunction, with no change in plasma norepinephrine. In the myocardium, we identified 109 differentially expressed proteins involved in calcium pathways, cholesterol metabolism, and galactose metabolism. Notably, we found that calmodulin, a key protein of intracellular calcium signaling, was significantly upregulated by GBP in the heart but not in the brain. In summary, we found that acute and chronic GBP treatments suppressed cardiovascular function in rats, which is attributed to abnormal calcium signaling in cardiomyocytes. These data reveal a novel side effect of GBP independent of the nervous system, providing important translational evidence to suggest that GBP can evoke adverse cardiovascular events by depression of myocardial function.https://www.mdpi.com/2073-4409/12/23/2705gabapentinarterial blood pressureheart rateleft ventricular functionproteomicsbioinformatics |
| spellingShingle | Ved Vasishtha Pendyala Sarah Pribil Victoria Schaal Kanika Sharma Sankarasubramanian Jagadesan Li Yu Vikas Kumar Chittibabu Guda Lie Gao Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats Cells gabapentin arterial blood pressure heart rate left ventricular function proteomics bioinformatics |
| title | Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats |
| title_full | Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats |
| title_fullStr | Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats |
| title_full_unstemmed | Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats |
| title_short | Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats |
| title_sort | effects of acute and chronic gabapentin treatment on cardiovascular function of rats |
| topic | gabapentin arterial blood pressure heart rate left ventricular function proteomics bioinformatics |
| url | https://www.mdpi.com/2073-4409/12/23/2705 |
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