Experimental Study On "Time—efficacy" Relationship Of Blood Pressure Induced By Aconite

Objective:To determination of Aconitum alkaloids in the different components of Aconite and estalblish a method for the determination of six kinds of Aconitum alkaloids in Aconitum carmichaeli and its samples.To compare the pharmacologic effects of the different components of Aconite with dosages of different convertsion criteria.Methods:C18 column was used,and acetonitrile-tetrahydrofuran(25:15) as the mobile phase A, 0.1mol·L-1 NH4 AC solution as the mobile phase B,gradient elute with a flow rate of 1.0mL·min-1 and a detection wavelength of 235 nm. According to the Pharmacopoeia and acute toxicity to prepare the all-comperents, water extracted comperents and alcohol extracted comperents,and rats were given all-comperents, water extracted comperents and alcohol extracted comperents by gavage respectively. Changes of rat blood pressure according to different time and dose were observed in 15, 30, 60, 90,120 min respectively by BP-100 A automatic mouse non-invasive blood pressure measurement system. According to the Pharmacopoeia and acute toxicity to prepare the all-comperents, water extracted comperents and alcohol extracted comperents.The model of hypotension was replicated by blood-letting. The curves of blood pressure was recorded during experiment by physiological polygram and detected the contents of serum LDH、CK to study the blood pressure influences of “dose-time-efficacy” relationship via a single administration on all-comperents, water extracted comperents and alcohol extracted comperents.Results:The six kinds of Aconitum alkaloids were separated,and calibration curves of them were in good linearity over the certain range respectively. The all-comperents,water extracted comperents and alcohol extracted comperents of Aconite with proper dosage could elevate blood pressure in normal and blood-letting hypotension rats, and there is a certain relationship of “dose-time-efficacy”. Different components of Aconite could elevate blood pressure,and alcohol extracted comperents are with the greatest degreeof effect followed by the water extracted comperents,and least is the all-comperents.Different components of Aconite in highest dosage had different changes during 120 min as side-effect were noted and increased obvipusly the serum content of LDH and CK of the rats when high dosage was used.Conclusion:The research established a simple and effective HPLC method for the determination of six kinds of Aconitum carmichaeli and its samples. The different components of Aconite with proper dosage could elevate blood pressure in normal and blood-letting hypotension rats, and there is a certain relationship of “dose-time-efficacy”.However,as enhanced effects obviously appeaved as the dosage increased,heart damage were noted when high dosage was used.The results suggest that we should pay more attention on the possible risk when increasing the dosage of Aconite in clinical practice.