选择性醛固酮受体拮抗剂对肾血管性高血压的作用及机制

Effect and mechanism of selective aldosterone receptor blocker eplerenone on renovascular hypertensive rats

目的 研究选择性醛固酮受体拮抗剂eplererNONE(EP)对肾血管性高血压的作用机制。方法 Wistar大鼠48只,随机分6组,1组为假手术组,其余5组均为2K-1C肾血管性高血压模型,再分为对照组、EP早给药组、EP晚给药组、洛沙坦(LO)早给药组和LO晚给药组。实验前及术后每2周检测收缩压(SBP)及尿蛋白排泄率(UPE)。对主动脉、心脏及肾脏进行病理组织学检查及一氧化氮合酶(ecNOS)基因表达的分析。结果 与假手术组比较,第10周对照组收缩压(SBP)明显增加;LO及EP早给药组SBP明显降低;LO及EP晚给药组SBP没有明显降低。与假手术组比较,对照组大鼠出现明显蛋白尿;LO早给药组和EP早给药组蛋白尿明显减少(P<0.05及P<0.01);LO及EP晚给药组蛋白尿没有明显降低。与对照组比较,EP早给药组明显增加心脏ecNOS基因表达;两EP给药组主动脉ecNOS基因表达明显增加;两LO给药组对心脏及主动脉ecNOS基因表达无明显影响;LO早给药组及两EP给药组肾脏ecNOS基因表达明显增加。结论 EP早期给药治疗明显降低2K-1C肾血管性高血压大鼠的收缩压和蛋白尿,其机制可能与心、肾、主动脉ecNOS基因表达上调有关。

Objective To study the effect and mechanism of a selective aldosterone receptor blocker, eplerenone (EP), on renovascular hypertensive rats. Method Forty-eight Wistar rats were divided into six groups: sham operation group, control model group, early EP group, late EP group, early losartan (LO) group and late LO group. Systolic blood pressure (SBP) and urinary protein excretion (UPE) were measured before and every two weeks after operation. Histopathology and endothelial cell nitric oxide synthase (ecNOS) gene expression were examined in heart, aorta and kidney. Results SBP obviously increased in control model group as compared to sham group at week 10(132. 1 ±2.4 vs. 115.0±0.6 mmHg, P = 0. 0191), while early treatment with LO or EP could decrease SBP significantly as compared to control group. The control group developed significant UPE [ (21. 7 ± 1.9) mg/d] compared with the sham group [(13. 4±0. 8) mg/d] (P < 0.05), while early treatment with LO or EP could decease UPE significantly. As compared to control group, ecNOSmRNA expression of heart tissue was significantly increased in early EP group (0. 47 ± 0.01 vs. 0.43±0.01, P < 0.05). The expression of ecNOSmRNA in aorta tissue significantly elevated in two EP groups. LO did not influence the ecNOSmRHA expression in heart and aorta. The expression of ecNOSmRNA in renal tissue significantly up-regulated in early LO group and two EP groups compared with control group (0. 22 ±0. 01, 0. 22 ± 0. 02 vs. 0. 15 ±0. 01, P < 0. 05 respectively) . Conclusion Early EP treatment can decrease SBP and urinary protein, whose mechanism may be related to the up-regulation of ecNOSmRNA expression in heart, aorta and renal tissue.