洛沙坦对血管紧张素Ⅱ诱导的心肌细胞c-fos表达及对细胞内游离钙升高的拮抗作用

目的 研究血管紧张素AT₁亚型受体拮抗剂洛沙坦(losartan,LT)对血管紧张素Ⅱ(AngⅡ)诱导的心肌细胞c-f os 表达及细胞内游离钙变化的影响。方法 斑点杂交及Fura-2技术。结果 AngⅡ10nmo l/L 能诱导培养乳鼠心肌细胞c-fos的一过性高表达及Ca²⁺] 的显著升高。LT 20μmol/L能显著抑制AngⅡ诱导的心肌细胞c-fos的高表达,而血管紧张素AT₂亚型受体拮抗剂PD123319 则无明显作用。LT1~100μmol/L 能剂量依赖性地抑制AngⅡ引起的Ca²⁺]i升高。结论 AngⅡ诱导的心肌细胞c-f os 高表达及Ca²⁺]i升高可能是通过AT₁亚型受体介导而实现的,LT可能是一种治疗心肌肥厚的有效药物。

Inhibitory effects of Losartan on c-fos expression and intracellular free calcium elevation induced by Angiotensio Ⅱ in cardiomyocytes of neonatal rats

Aim To study effects of Losartan on c-fos mRNA expression and free int racellular Ca²⁺( Ca²⁺] i)level induced by AngiotensionⅡ(AngⅡ)in cardiomyocytes of neo natalrats.Methods Effect of Losartan on c-fos mRNA ex pression induced by AngⅡin cardiomyocytes was studied with dot blotting assay.Ca²⁺was measured with Ca²⁺sensitive fluorescent indicator (Fura-2/AM) using AR-C M-M IE cation measurement system.Results AngⅡtemporally induced c-fos gene expression and significantly increased the Ca²⁺] ielevation in cardiomyocytes of neonatal rat s.However,the dynamic changes of c-fosgene expression and Ca²⁺] i could be inhibited by Losartan 20μmol/L,but not by PD123319.Lo sartan 1~100μmol/L significantly inhibited AngⅡinduced Ca²⁺] ielevation in adose-dependent manner.Conclusion The results suggest that c-fos expression andCa²⁺] ielevation induced by AngⅡare mediated by AT₁ subtype acceptor.Losartan maybe an effective drug in treating cardiac hypertrophy.