Losartan reduced connexin43 expression in left ventricular myocardium of spontaneously hypertensive rats

• Published in: Journal of Zhejiang University. B. Science 2008-06, Vol.9 (6), p.448-454
• Main Authors: Zhao, Li-li, Chen, Hong-juan, Chen, Jun-zhu, Yu, Min, Ni, Yun-lan, Zhang, Wei-fang
• Format: Article
• Language: English
• Subjects: Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Biomedical and Life Sciences; Biomedicine; Blood Pressure - drug effects; Blotting, Western; Connexin 43 - metabolism; Hypertension - drug therapy; Hypertension - metabolism; Hypertension - physiopathology; Hypertrophy, Left Ventricular - drug therapy; Hypertrophy, Left Ventricular - metabolism; Hypertrophy, Left Ventricular - pathology; Losartan - pharmacology; Male; Myocardium - metabolism; Natriuretic Peptide, Brain - blood; Proteins; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rodents; Transcription Factor RelA - metabolism; 左心室; 心肌膜; 连接蛋白; 高血压
• ISSN: 1673-1581; 1862-1783
• DOI: 10.1631/jzus.B0820050

Objective： To assess the effect of angiotensin II type 1 （AT1） receptor antagonist losartan on myocardium connexin43 （Cx43） gap junction （GJ） expression in spontaneously hypertensive rats （SHRs） and investigate possible mechanisms. Methods： Sixteen 9-week-old male SHRs and 8 age-matched male Wistar-Kyoto （WKY） rats were included in this study. SHRs were randomly divided into two groups to receive losartan at 30 mg/（kg·d） by oral gavage once daily for 8 weeks （SHR-L） or vehicle （0.9% saline） to act as controls （SHR-V）; WKY rats receiving vehicle for 8 weeks served as normotensive controls. At the end of the experiment, rats were sacrificed and the hearts were removed. Expressions of Cx43 and nuclear factor-kappaB p65 （NF-κB p65） proteins in all three groups were observed and further investigations on the effect of angiotensin II type 1 receptor antagonist losartan （30 mg/（kg·d）, 8 weeks） on Cx43 expression were conducted with Western blot and immunohistochemistry. NF-κB p65 protein in nuclear extracts was determined by Western blot. Results： Left ventricular （LV） hypertrophy was prominent in SHRs, Cx43 and NF-κB p65 protein expressions were obviously upregulated and Cx43 distribution was dispersed over the cell surface. Treatment with losarton reduced the over-expressions of Cx43 and NF-κB p65 in LV myocardium. The distribution of Cx43 gap junction also became much regular and confined to intercalated disk after losartan treatment. Conclusion： Cx43 level was upregulated in LV myocardium of SHR during early stage of hypertrophy. Angiotensin II type 1 receptor antagonist losartan prevented Cx43 gap junction remodeling in hypertrophied left ventricles, possibly through the NF-κB pathway.