Acetaminophen treatment evokes anticontractile effects in rat aorta by blocking L-type calcium channels

Correia, Mikaelle Costa; Santos, Eder S. A.; Neves, Bruno Junior; Rocha, Matheus Lavorenti

Acetaminophen treatment evokes anticontractile effects in rat aorta by blocking L-type calcium channels

Data

2022

Autores

Correia, Mikaelle Costa

Santos, Eder S. A.

Neves, Bruno Junior

Rocha, Matheus Lavorenti

Resumo

Background Acetaminophen (APAP) is the most widely used analgesic and antipyretic in the world. However, in high or continuous doses, it can cause serious side effects including blood pressure variability and cardiovascular injuries, which are barely explored. This study aimed to evaluate the acute effect of APAP treatment on vascular tone focused on the blocking of Ca2+ channels. Methods Rats were treated with APAP orally by gavage (500 mg/kg/single dose). After 12 h, the aorta was isolated for vascular reactivity studies in an isolated organ bath. Vascular contraction and relaxation were measured after different stimuli. Moreover, molecular docking studies were performed to evaluate the action of NAPQI (APAP metabolite) on L-type calcium channels. Results Phenylephrine-induced maximal vascular contraction was reduced in the APAP group (138.4 ± 9.2%) compared to the control group (172.2 ± 11.1%). APAP treatment significantly reduced contraction induced by Ca2+ influx stimulated with phenylephrine or KCl and reduced contraction mediated by Ca2+ released from the sarcoplasmic reticulum induced by caffeine. There was no difference in vascular relaxation induced by acetylcholine or sodium nitroprusside. Computational molecular docking demonstrated that NAPQI is capable of blocking L-type Ca2+ channels (Cav1.2), which would limit the influx of Ca2+. Conclusion These results suggest that APAP treatment causes an anticontractile effect in rat aorta, possibly by blocking the influx of Ca2+ through L-type channels (Cav1.2).

Citação

CORREIA, Mikaelle C.; SANTOS, Eder S. A.; NEVES, Bruno J.; ROCHA, Matheus L. Acetaminophen treatment evokes anticontractile effects in rat aorta by blocking L-type calcium channels. Pharmacological Reports, Berlin, v. 74, n. 3, p. 493-502, 2022. DOI: 10.1007/s43440-022-00367-y. Disponível em: https://link.springer.com/article/10.1007/s43440-022-00367-y. Acesso em: 5 set. 2024.