Changes Of Large-conductance Calcium-activated Potassium Channels In Vascular Smooth Muscle Cells Derived In The Saltsensitive Hypertensive Rat Model Induced By Sensory Denervation

Objective:The experiment is to observe the blood pressure and the current density of largeconductance calcium- activated potassium channel(BKCa) in vascular smooth muscle cells( VSMC) in the salt- sensitive hypertensive rat by injuring sensory nerve. as well as to explore the pathogenesis of hypertension with high salt. Methods:1. To establish the model of salt sensitive hypertension rats. Newborn male SD rats were randomly divided into A and B group with 75 rats each, on the 1st and 2nd day of life.A group were given 50 mg/kg capsaicin,B group were treated with equal volumes of vehicle solution. After the weanling period,rats were divided into 4 groups and subjected to the followings for 16 weeks: The normal control group(fed with 0.5%Na Cl diet)30 rats; High salt group(the diet containing 4%Na Cl)30 rats; CAP group(injection of CAP and give 0.5%Na Cl containing diet 30 rats; Model group(injection of capsaicin and give 4%Na Cl containing diet)30 rats.2. The blood pressure of rats was measured. Indirect tail- cuff systolic blood pressures was measured at 4th, 8th, 12 th, 16 th weeks.3. Record the BKCa current.The model rats and control rats were sacrificed at 4、 8、12 and 16 week.Single aortic vascular smooth muscle cells of rats were obtained by enzymatic dissociation.Then,to record the BKCa current of VSMC in each group by the whole cell patch clamp technique. Results:1.SBP of Model group were significantly increased compared with others(P<0.01), at 4 th,8 th,12 th,16 th weeks,compared with normal contrlo group, the SBP respectively were( 141±5.0 vs.108±4.0)、( 155±6.0 vs.110±3.0)、( 168±6.0 vs.109±4.0)、(179±7.0 vs.108±5.0)mm Hg.Compared with others, SBP of the high salt group had statistical significance(P<0.01),at12 th and16 th weeks.2.The BKCa current and BKCa peak current density of model group were increased as the time of high salt diet, compared with others,the BKCa peak current density of Model group were significantly increased(P<0.01), at 4th, 8th, 12 th, 16 th weeks, compared with normal contrlo group, the BKCa peak current density respectively were(126.05±4.73 vs.83.69±4.38)、(160.69±5.07 vs. 84.79±4.32)、(201.87±4.98 vs. 85.84±4.16)、(231.79±4.97 vs. 86.92±4.19). Compared with others, BKCa peak current density of high salt group had statistical significance,(P<0.01),at 12 th and16 th weeks. Conclusion:(1) The salt-sensitive hypertensive rat model induced by sensory denervationwas successfully established by injecting capsaicin and high salt diet.(2) The BKca peak current density in aortic vascular smooth muscle cells of model rats was significantly increasing with the duration of the time of high salt and the rising of blood pressure;(3) The VSMCs relaxation caused by increased BKCa current density cannot counteract myogenic tone of artery,which contributes to genesis and development of chronic hypertension.