title: A conscious rat model involving bradycardia and hypotension after oral administration: a toxicokinetical study of aconitine.
abstract: 1. A model of aconitine-induced bradycardia and hypotension, which is similar to aconitine poisoning in humans, was constructed in conscious rats by oral administration. 2. Blood pressure (BP) and heart rate (HR) of Sprague-Dawley rats were measured using a volume pressure recording (VPR) system. The pharmacokinetics of toxic doses of aconitine and its metabolites were analyzed using UPLC-MS/MS. 3. The HR was significantly decreased by 29% at 2 h after oral administration of 200 μg/kg aconitine. When the dose was increased to 400 μg/kg, systolic BP and diastolic BP were significantly decreased by 11% and 12% at 2 h after the administration, except when bradycardia occurred at 2 h and 4 h. The drug concentration-time curve showed a double-peak phenomenon in rats administered a 400 μg/kg dose. The AUC0-12 hvalue in the 400 μg/kg group significantly increased 0.8-fold compared to the 200 μg/kg group. Moreover, a high plasma concentration of 16-O-demethyaconitine was found in the rats that received two toxic doses. 4. In conclusion, bradycardia and hypotension are induced in conscious rats by a toxic dose of aconitine (400 μg/kg), and there was no significant difference in dose-normalized AUC0-12 hvalues between oral administrations of 200 μg/kg and that of 400 μg/kg. However, the dose-normalized Cmaxand AUC0-12 hvalues in 200 μg/kg and 400 μg/kg groups were significantly smaller than those in 100 μg/kg group. The metabolites of aconitine, 16-O-demethyaconitine, and benzoylaconitine may also contribute to the hypotensive response.
authors.affiliation: a School of Chinese Integrative Medicine, Hebei Medical University , Shijiazhuang , China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: a School of Chinese Integrative Medicine, Hebei Medical University , Shijiazhuang , China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Kong
authors.affiliation: a School of Chinese Integrative Medicine, Hebei Medical University , Shijiazhuang , China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Du
authors.affiliation: a School of Chinese Integrative Medicine, Hebei Medical University , Shijiazhuang , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: a School of Chinese Integrative Medicine, Hebei Medical University , Shijiazhuang , China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: a School of Chinese Integrative Medicine, Hebei Medical University , Shijiazhuang , China.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: a School of Chinese Integrative Medicine, Hebei Medical University , Shijiazhuang , China.
authors.forename: Tonghui
authors.initials: T
authors.lastname: Li
authors.affiliation: a School of Chinese Integrative Medicine, Hebei Medical University , Shijiazhuang , China.
authors.forename: Leiming
authors.initials: L
authors.lastname: Ren
mesh_terms: D000157:Aconitine / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001919:Bradycardia / Q000139:chemically induced*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D007022:Hypotension / Q000139:chemically induced*; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D061585:Voltage-Gated Sodium Channel Agonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D061585:Voltage-Gated Sodium Channel Agonists; D000157:Aconitine
keywords: Aconitine; bradycardia; conscious rat; hypotension; toxicokinetics