The Relationship Between Voltage-gated Calcium Channels Subtypes And The Locus Coeruleus Secretion By Stress Induced Hypertension Model Rats

Objective:The role of central nervous system dysfunction in the pathogenesis of hypertension has long been known.Mental stress can lead to the excitement and inhibition of the cerebral cortex,which induced dysfunction of the central nervous system.Voltage-gated calcium channels are widely involved in the regulation of central nervous system neurotransmitter release,but how does each sub type of voltage-gated calcium channels influence the hypothalamus noradrenaline release projected from locus coeruleus in stress-induced hypertensive rats has not been reported previously.To explore the effects of voltage gated calcium channel blockers(VGCC)on neurotransmitter release in the locus coeruleus,stress-induced hypertensive model rats were used to analysis the central mechanism of voltage gated calcium channel subunits involved in the pathogenesis of hypertension,which will help us to further clarify the mechanism of sub type of voltage-gated calcium channels affect the secretion of norepinephrine(NE)in stress-induced hypertensive rats,and provide experimental basis to study anti-hypertension drugs.Methods: 66 male clean grade Sprague-Dawley(180-200g)rats(SD)were used during the three rounds of experiments.There were 22 rats in each round experiment.22 rats were randomly divided into two groups: stress group(n=12)and control group(n=10).The hypertension model group rat was established by combining noise and foot-shock stresses.Blood pressure of rats was measured by tail cuff method.After the end of modeling,NE release in the hypothalamus by electrical stimulation in locus coeruleus(LC)was recorded by carbon fiber electrode.The effect of nifedipine and ralfinamide mesylate was studied in three round experiments.The peak value,the time to peak and half-life period of NE signal in both group rats were analyzed.Results: After 20 days of stress,the blood pressure of model group rats was significantly increased(112.0 ± 4.8 mm Hg vs 147.0 ± 12.1 mmHg,n=36,P <0.01),while the blood pressure of the control group remained unchanged.When the locus coeruleus was electrically stimulated,NE release in the hypothalamus was more in model group rats than that in control group rats by using carbon fiber microelectrode recording technique.the peak value of NE release increases(187.9±47.9 pA,n=24,vs127.6 ± 39.68 pA,n=15,P <0.05),the time to peak and half-life period of NE signal have no statistical difference between two groups.30 min after intraperitoneal injection of nifedipine(1 mg / kg),The peak value of NE signal and blood pressure decreased in model group rats(The peak value of NE signal : 81.3 + 27.1 pA vs138.1 + 29.7pA,n = 6,P < 0.05;(blood pressure : 99.5±22.5 mmHg vs 89.3±4.8 mmHg,n=6,P <0.01)),but no change was presented in control group rats.No significant changes of the time to peak and half-life period of NE signal were recorded in both group rats.30 min after intracerebroventricular injection of nifedipine(1mg / ml,5 μg),the peak value of NE signal and blood pressure decreased in the model group rats(peak value : 113.5 + 15.6pA vs 208.7 + 19.96 pA,n = 8,P < 0.01;blood pressure : 112.4±9.1mmHg vs 88.1±14.5 mmHg,n=4,P <0.05)),but no statistical change was presented in control group rats.No significant changes of the time to peak and half-life period of NE signal were recorded in both group rats.30 min after intracerebroventricular injection of Ralfinamide Mesylate(1 mg / ml,10 μg),the peak value of NE signal and blood pressure decreased in the model group rats(peak value : 105.3± 33.8 PA vs 197.2± 60.4 PA,n = 10,P < 0.05;blood pressure :115.3±6.0 mmHg vs 100.1±12.4 mmHg,n=8,P <0.05)),no statistical change was presented in control group rats.No significant changes of the time to peak and half-life period of NE signal were recorded in both group rats.Conclusion:1.The blood pressure of model group rats was significantly higher than that of the control group rats.2.After electrical stimulation of the locus coeruleus,the NE signal detected in the hypothalamus of model group rats was higher than that in the control group rats.3.N-type of voltage gated calcium channel blockers reduce the blood pressure and the peak value of the NE signal in stress-induced hypertension rats through intracerebroventricular injection.4 L-type of voltage gated calcium channel blockers reduce blood pressure in hypertensive rats,and decrease the peak value of NE signal detected by hypothalamic nucleus whatever the blocker was administered by intraperitoneal injection or lateral ventricle administration.