非洛地平缓释片及缬沙坦对感觉神经损伤性盐敏感性高血压大鼠的降压作用及其机制探讨

The effect and mechanism of felodipine and valsartan on a novel salt-sensitive hypertensive rat induced by sensory denervation

目的 观察非洛地平缓释片、缬沙坦对感觉神经损伤性盐敏感性高血压大鼠的作用,探讨其作用机制及该模型形成的机制。方法 新生Wistar大鼠皮下注射辣椒辣素 (50mg/kg),对照组大鼠注射对照液,哺乳期后挑选出雄性大鼠分成 5组分别给予含盐不同的饮食及非洛地平、缬沙坦(30mg/kg每天,灌胃)干预 4周,检测鼠尾收缩压、体重、淋巴细胞胞浆游离钙 ( [Ca^(2+ )]i)、血浆降钙素基因相关肽、血管紧张素Ⅱ、内皮素浓度和 24h饮水量、尿量、尿钠、尿钾。结果 非洛地平及缬沙坦干预组鼠尾收缩压、淋巴细胞[Ca^(2+ ) ]i明显低于辣椒辣素+高盐组;缬沙坦干预组血浆血管紧张素Ⅱ浓度明显高于其余各组,鼠尾收缩压低于非洛地平干预组;非洛地平干预组淋巴细胞 [Ca^(2+ )]i低于缬沙坦干预组,肾排钠量高于辣椒辣素+高盐组及缬沙坦干预组。结论 非洛地平及缬沙坦干预能阻止辣椒辣素处理大鼠在高盐饮食时血压及淋巴细胞 [Ca^(2+ ) ]i升高,提示该模型的形成可能与肾素血管紧张素系统及细胞内钙超载有关,而与肾素血管紧张素醛固酮系统关系可能更密切。

Objective To investigate the effect and mechanism of valstartan and felodipine extended release tablets (Plendil) on a novel salt sensitive hypertensive rat induced by sensory denervation Methods Newborn Wistar rats were given 50 mg/kg capsaicin subcutaneously on the 1st and 2nd day of life Control rats were treated with vehicle solution(10%ethanol,10%Tween 80 in salin) After weanling period(3 weeks), male rats were divided into 5 groups and subject to the following treatment for 4 weeks: control + high salt diet(4%, CON HS), capsaicin + normal salt diet(0 5%, CAP NS), capsaicin + high salt diet (CAP HS), capsaicin + high salt diet + Valstartan (30 mg/kg per day, by orally) (CAP HS VAL),capsaicin + high salt diet + Plendil(30 mg/kg per day, by orally) (CAP HS PLE) Tail cuff systolic blood pressure , body weight, intralymphocytic [Ca 2+ ] i, plasma calcitonin gene related peptide concentration ([CGRP]), angiotensin Ⅱ concentration([AngⅡ] ) and 24 hour water intake, urinary volume, urinary Na + and K + concentrations were examined Results Tail cuff systolic blood pressure and intralymphocytic [Ca 2+ ] i were lower in CAP HS VAL or CAP HS PLE group than those in CAP HS group Plasma [AngⅡ] were higher in CAP HS VAL group than that in other groups Tail cuff systolic blood pressure were lower in CAP HS VAL group than that in CAP HS PLE group Intralymphocytic [Ca 2+ ] i were lower in CAP HS PLE group than that in CAP HS VAL group The 24 hour urine sodium excretion was higher in CAP HS PLE group than that in CAP HS or CAP HS VAL group Conclusion Valstartan or Plendil could prevent the development of salt sensitive hypertension induced by sensory denervation and the overloading of intracellular [Ca 2+ ] i, which indicated that salt sensitive hypertension induced by sensory nerve degeneration might be related to renin angiotensin aldosterone system (RAAS) and the over loading intracellular [Ca 2+ ] i, and might be more closely to RAAS