厄贝沙坦对肾性高血压大鼠左心室肥厚心肌腺苷三磷酸酶和钙调神经磷酸酶的影响

Effects of Irbesartan on ATPase and Calcineurin in Myocardial Tissue from Renovascular Hypertension Rat

目的观察厄贝沙坦对肾性高血压大鼠(RHR)心肌组织Na+-K+腺苷三磷酸酶(ATPase)、Ca2+-ATPase和钙调神经磷酸酶(CaN)及心肌肥厚指标的影响。方法采用两肾一夹制造肾血管性高血压模型,21只大鼠随机分为肾性高血压大鼠模型组(RHR)、厄贝沙坦组[50mg/(kg.d)]和假手术组,每组7只;测量各组大鼠术前、术后及用药后血压;用药8周后,测量大鼠左心室质量/体质量(LVM/BM)、左心室心肌细胞横径(TDM),采用生物酶学方法检测心肌Na+-K+-ATPase、Ca2+-ATPase、CaN活性。结果与假手术组比较,RHR模型组血压、LVM/BM、TDM均显著增高,心肌Na+-K+-ATPase和Ca2+-ATPase活性明显降低,CaN活性升高;厄贝沙坦能降低RHR血压、LVM/BM、TDM,增加RHR心肌Na+-K+-ATPase活性[RHR模型组(6.83±0.80)比厄贝沙坦组(9.53±1.03)μmolPi/(h.mgpro),P<0.01]和Ca2+-ATPase活性[RHR模型组(6.47±0.77)比厄贝沙坦组(8.06±0.53)μmolPi/(h.mgpro),P<0.01],降低CaN活性[RHR模型组(0.91±0.08)比厄贝沙坦组(0.72±0.05)μmolPi/(h.mgpro),P<0.01]。结论厄贝沙坦可能通过增加心肌Na+-K+-ATPase、Ca2+-ATPase活性和抑制CaN活性,从而减轻肾血管性高血压大鼠左心室肥厚。

Objective To investigate the effects of irbesartan on Na^＋-K^＋-ATPase, Ca^2＋-ATPase and Calcineurin（CaN） in myocardial tissue and cardiac hypertrophy in renovascular hypertensive rats （RHR）. Methods The renovascular hypertension was induced by two kidney-one clip method. Twenty-one male Sprague-Dawley rats were randomly divided into three groups： RHR model group（n： 7）, irbesartan treated group [50 mg/（kg · d） （n=7）], and sham operation group （n=7）. Blood pressure was measured before and after operation. The ratio of left ventrieular mass and body mass（LVM/BM）, and the transverse diameter of myocytes（TDM） of left ventricle（LV） were calculated; the activities of Na^＋-K^＋-ATPase, Ca^2＋-ATPase and CaN of LV were measured by biochemistry and enzymology. Results Compared to the sham operation group, systolic blood pressure（SBP）,LVM/BM, TDM, CaN activity in RHR were increased, with concomitanltly decreases in the activities of Na^＋- K^＋-ATPase, Ca^2＋-ATPase. Irbesartan significantly decreased the SBP, LVM/BM, TDM and increased the activities of Na^＋-K^＋-ATPase [RHR （6.83±0.80） vs irbesartan （9.53±1.03）μmol Pi/（h · mg pro）, P〈0.01] and Ca^2＋-ATPase[RHR （6.47±0.77） vs irbesartan （ 8. 06 ± 0. 53 ） μmol Pi/（h. mg pro）, P〈0.01], and inhibited CaN activity [RHR （0.91±0.08） vs irbesartan （0.72±0.05）/,mol Pi/（h · mg pro）, P〈0.01]. Conclusion Irbesartan reversed left ventricular hypertrophy associated with increases in activities of myocardial Na^＋- K^＋-ATPase, Ca^2＋ ATPase and decreases in CaN activity.