| KCNQ gene encoded Kv7 potassium ion channel,widely distributed in the nerve and cardiovascular system,QO-83 is a Kv7 channel has a strong open activity of small molecular compounds,is expected to develop into the treatment of epilepsy,pain and other drugs.This topic focuses on the possible effects of QO-83 on the cardiovascular system when treating neuropsychiatric disorders.Objective: To observe the effect of QO-83 on blood pressure,heart rate and electrocardiogram in rats and dogs,analyze the effect on the alien blood vessels,and explore the mechanism of action.Methods:1.SD rats were randomly divided into 5 groups,and abdominal injections were given four doses of soluble media,QO-83 compounds,0.25mg/kg,0.5 mg/kg,1 mg/kg and 2 mg/kg,respectively,to compare the changes in blood pressure,heart rate and electrocardiogram in anaesthetic rats.2.Intravenous injection after anaesthetic in Beagle dog,intravenous QO-83 compound 0.4 mg/kg,0.8 mg/kg,to observe the changes in animal blood pressure,heart rate and electrocardiogram before and after administration.3.After inhalation of anesthesia in SD rats,the abdominal cavity was injected with QO-83 compounds 0.5 mg/kg,1 mg/kg,and changes before and after the administration of cardiovascular parameters and intravascular diameter were observed by ultrasound in small animals.4.After the anesthetic rats were given the nerve section blocker hexamethamine and choline receptor blocker Atopin,respectively,the effects of QO-83 on blood pressure,heart rate and electrocardiogram at 0.5 mg/kg and 1 mg/kg were observed.5.Take the aorta and intestinal membrane artery of rats,observe the effect of KCl,PE and 4-AP prestriction of blood vessels in the off-body,and compare the vascular tension in the range of 1 μmol/L to 100 μmol/L concentration in the case of epithelial and endothelial integrity.Results:1.QO-83 reduced blood pressure and heart rate in SD rats with dose dependence at 0.25 mg/kg,0.5 mg/kg,1 mg/kg,2 mg/kg After administration systolic pressure(SBP),diastolic pressure(DBP),average pulse pressure(MBP)decreased significantly(P <0.05,0.01,0.01),with significant differences in heart rate decrease(P<0.05,0.01,0.01),significantly longer and significant differences(P<0.05)at 2mg/kg.2.QO-83 reduced the blood pressure and heart rate of beagle dogs with dose dependence at 0.2mg/kg,0.4mg/kg,0.8mg/kg,SBP(0.2,0.4,0.8mg/kg),DBP(0.4,0.8mg/kg),MBP(0.4,0.8mg/kg)decreased after administration There were significant differences(P<0.05,0.05,0.01),a significant difference in heart rate(0.8 mg/kg dose)(P<0.05),and no significant difference in electrocardiograms.3.Ultrasound results showed that SD rats had significant inhibition effects on the heart rate(HR),blood fraction(EF),and output per beat(SV)after 30 min injections in the abdominal cavity at doses of 0.5 mg/kg and 1mg/kg P<0.01,0.05,0.05),female rats were more pronounced than male rats;4.The inhibition of blood pressure and heart rate(P<0.01,0.05)by blocking nerve sections and atopin in advance with ammonium hexamethamide can significantly reduce QO-83(0.5 mg/kg,1 mg/kg dose).5.QO-83 in the range of 1 to 30 μmol/L concentration of KCl,4-AP,PE caused by rats off the body aorta,enteroline membrane artery,whether de endothelial and non-endothelial blood vessel contraction is not significantly alleviated.The prestriction of the small arteries of the intestinal membrane induced by PE at 100 μmol/L has a soothing effect and there are significant differences(P<0.05).Conclusion: QO-83 as a new Kv7 potassium channel open agent has an overcurrent antihypertensive effect,its effect is not by directly activating the KCNQ4 channel to expand blood vessels,may be through the opening of SCG neurons on the M-current,resulting in a decrease in the sensing nerve tension caused. |
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