Pendyala, V.V.; Pribil, S.; Schaal, V.; Sharma, K.; Jagadesan, S.; Yu, L.; Kumar, V.; Guda, C.; Gao, L. Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats. Cells2023, 12, 2705.
Pendyala, V.V.; Pribil, S.; Schaal, V.; Sharma, K.; Jagadesan, S.; Yu, L.; Kumar, V.; Guda, C.; Gao, L. Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats. Cells 2023, 12, 2705.
Pendyala, V.V.; Pribil, S.; Schaal, V.; Sharma, K.; Jagadesan, S.; Yu, L.; Kumar, V.; Guda, C.; Gao, L. Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats. Cells2023, 12, 2705.
Pendyala, V.V.; Pribil, S.; Schaal, V.; Sharma, K.; Jagadesan, S.; Yu, L.; Kumar, V.; Guda, C.; Gao, L. Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats. Cells 2023, 12, 2705.
Abstract
Gabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant to treat partial seizures and neuropathic pain. While a majority of the side effects are associated with the nervous system, emerging evidence suggests a high risk for heart diseases in the patients taking GBP. In the present study, we used a preclinical model of rats to investigate (1) the acute cardiovascular responses to GBP (bolus i.v. injection, 50 mg/kg) and (2) the effects of chronic GBP treatment (i.p. 100 mg/kg/day x 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 experiment (1), we found that i.v. 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 (*p < 0.05 and **p < 0.01 vs baseline; n = 4/group). In experiment (2), 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. Particularly, 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.
Medicine and Pharmacology, Anesthesiology and Pain Medicine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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