摘要
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_fos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AngⅡ10nmol/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。LT20μmol/L能显著抑制Ang Ⅱ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Ang Ⅱ诱导的心肌细胞c_fos高表达及[Ca2 + ]i升高可能是通过AT1 亚型受体介导而实现的 。
Aim To study effects of Losartan on c_fos mRNA expression and free intracellular Ca2+(i) level induced by Angiotension Ⅱ(AngⅡ) in cardiomyocytes of neonatal rats . Methods Effect of Losartan on c_fos mRNA expression induced by Ang Ⅱ in cardiomyocytes was studied with dot blotting assay. Ca2+ was measured with Ca2+sensitive fluorescent indicator (Fura_2/AM) using AR_CM_MIE cation measurement system. Results AngⅡ temporally induced c_fos gene expression and significantly increased the i elevation in cardiomyocytes of neonatal rats . However, the dynamic changes of c_fos gene expression and i could be inhibited by Losartan 20 μmol/L, but not by PD123319. Losartan 1?100 μmol/L significantly inhibited Ang Ⅱ induced i elevation in a dose_dependent manner. Conclusion The results suggest that c_fos expression and i elevation induced by AngⅡ are mediated by AT1 subtype acceptor. Losartan may be an effective drug in treating cardiac hypertrophy.
