Butylidenephthalide antagonizes cromakalim-induced depressor and tachycardiac responses in conscious normotensive rats

• Main Authors: Lin, Yu-Jing, 林育菁
• Other Authors: Ko, Wun-Chang
• Format: Others
• Language: zh-TW
• Published: 1994
• Online Access: http://ndltd.ncl.edu.tw/handle/91740151624991510339

碩士 === 台北醫學大學 === 醫學研究所 === 82 === 　　Cromakalim (BRL 34915), is an opener of ATP-sensitive potassium channel subtype which has been reported to be distinct from that of pancreatic islet β-cells, has potent blood pressure lowering effect. Nowadays, few blockers have been repored, except the well known oral sulfonylurea antidiabetic agents, such as tolbutamide and glibenclamide (GBC) etc. 　　An indirect cuff method was used to determine the systolic pressure and heart rate of conscious normotensive rats in this study. The intraperitoneal pretreatment of synthetic butylidemephthalide (Bdph), the most potent antispasmodic constituent found in the neutral oil of Ligusticum wallichii FRANCH., at a dose of 30 mg/kg for 30 min, similar to 4-aminopyridine (4-AP, 0.4 mg/kg, i.p.) and GBC (10 mg/kg, i.v.), significantly rightward shifted the log dose-depressor and -tachycardiac response curves of cromakalim. The median effective doses (ED50) of test group were significantly greater than those of control (vehicle) group. There was no significant difference between the maximal depressor responses of both two groups. So was the maximal tachycardiac reponses. Therefore, Bdph may competitively antagonize cromakalim. This antagonism appears so selective, because that the 30 min pretreatment of Bdph (30 mg/kg, i.p.) could not significantly affect the depressor and cardiac responses of prazosin (α1 adrenergic receptor antagonist) and clonidine (α2 adrenergic receptor agonist). It also could not significantly affect the pressor and tachycardiac responses of Bay K 8644. However, nifedipine (1 mg/kg, i.v.) could significantly inhibit the pressor effect of Bay K 8644 (0.03~0.1 mg/kg, i.v.) and the tachycardiac effect of Bay K 8644 (0.03~0.3 mg/kg, i.v.) 　　The above results suggest that Bdph (30 mg/kg, i.p.), similar to 4-AP (0.4 mg/kg, i.p.) and GBC (10 mg/kg, i.v.), may be a blocker of ATP-sensitive potassium channel subtype, which could antagonize the depressor and tachycardiac responses antagonize the depressor and tachycardiac responses of cromakalim. However, in the abscence of or before administration of cromakalim, they did not affect the systolic pressure and heart rate, because they are inactive when the ATP-sensitive potassium channel is not opened.