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Journal of Zhejiang University SCIENCE B 2008 Vol.9 No.6 P.448-454


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

Author(s):  Li-li ZHAO, Hong-juan CHEN, Jun-zhu CHEN, Min YU, Yun-lan NI, Wei-fang ZHANG

Affiliation(s):  Department of Cardiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China

Corresponding email(s):   zhangweifangicu@126.com

Key Words:  Connexin43 (Cx43), Left ventricular (LV) hypertrophy, Angiotensin II, Nuclear factor-kappaB p65 (NF-&kappa, B p65), Gap junction (GJ)

Li-li ZHAO, Hong-juan CHEN, Jun-zhu CHEN, Min YU, Yun-lan NI, Wei-fang ZHANG. Losartan reduced connexin43 expression in left ventricular myocardium of spontaneously hypertensive rats[J]. Journal of Zhejiang University Science B, 2008, 9(6): 448-454.

@article{title="Losartan reduced connexin43 expression in left ventricular myocardium of spontaneously hypertensive rats",
author="Li-li ZHAO, Hong-juan CHEN, Jun-zhu CHEN, Min YU, Yun-lan NI, Wei-fang ZHANG",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Losartan reduced connexin43 expression in left ventricular myocardium of spontaneously hypertensive rats
%A Li-li ZHAO
%A Hong-juan CHEN
%A Jun-zhu CHEN
%A Min YU
%A Yun-lan NI
%A Wei-fang ZHANG
%J Journal of Zhejiang University SCIENCE B
%V 9
%N 6
%P 448-454
%@ 1673-1581
%D 2008
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0820050

T1 - Losartan reduced connexin43 expression in left ventricular myocardium of spontaneously hypertensive rats
A1 - Li-li ZHAO
A1 - Hong-juan CHEN
A1 - Jun-zhu CHEN
A1 - Min YU
A1 - Yun-lan NI
A1 - Wei-fang ZHANG
J0 - Journal of Zhejiang University Science B
VL - 9
IS - 6
SP - 448
EP - 454
%@ 1673-1581
Y1 - 2008
PB - Zhejiang University Press & Springer
ER -
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-&kappa;b 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.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1] Cai, W., Ruan, L.M., Wang, Y.N., Chen, J.Z., 2006. Effects of angiotensin II on connexin43 of VSMCs in arteriosclerosis. J. Zhejiang Univ. Sci. B, 7(8):648-653.

[2] Dahlof, B., Devereux, R.B., Kjeldsen, S.E., Julius, S., Beevers, G., de Faire, U., Fyhrquist, F., Ibsen, H., Kristiansson, K., 2002. Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet, 359(9311):995-1003.

[3] Dodge, S.M., Beardslee, M.A., Darrow, B.J., Green, K.G., Beyer, E.C., Saffitz, J.E., 1998. Effects of angiotensin II on expression of the gap junction channel protein connexin43 in neonatal rat ventricular myocytes. J. Am. Coll. Cardiol., 32(3):800-807.

[4] Emdad, L., Uzzaman, M., Takagshi, Y., Honjo, H., Uchida, T., Severs, N.J., Kodama, I., Murata, Y., 2001. Gap junction remodeling in hypertrophied left ventricles of aortic-banded rats: prevention by angiotensin II type 1 receptor blockade. J. Mol. Cell. Cardiol., 33(2):219-231.

[5] Gupta, S., Purcell, N.H., Lin, A., Sen, S., 2002. Activation of nuclear factor-kappaB is necessary for myotrophin-induced cardiac hypertrophy. J. Cell Biol., 159(6):1019-1028.

[6] Hirotani, S., Otsu, K., Nishida, K., Higuchi, Y., Morita, T., Nakayama, H., Yamaguchi, O., Mano, T., Matsumura, Y., Ueno, H., 2002. Involvement of nuclear factor-kappaB and apoptosis signal-regulating kinase 1 in G-protein-coupled receptor agonist-induced cardiomyote hypertrophy. Circulation, 105(4):509-515.

[7] Jiang, Y.G., Jiang, R., Jin, J., Wang, H.P., Chen, J.H., 2006. Changes of gap junction in penile cavernous smooth muscle cells of hypertensive rats. Zhonghua Nan Ke Xue, 12(11):1010-1013 (in Chinese).

[8] Litchenberg, W.H., Norman, L.W., Holwell, A.K., Martin, K.L., Hewett, K.W., Gourdie, R.G., 2000. The rate and anisotrophy of impulse propagation in the postnatal terminal crest are correlated with remodeling of Cx43 gap junction pattern. Cardiovasc. Res., 45(2):379-387.

[9] Mondry, A., Svynghedauw, B., 1995. Biological adaptation of the myocardium to chronic mechanical overload. Molecular determinants of the autonomic nervous system. Eur. Heart. J., 16(Suppl. 1):64-73.

[10] Peters, N.S., Green, C.R., Poole-Wilson, P.A., Severs, N.J., 1993a. Reduced content of connexin43 gap junctions in ventricular myocardium from hypertrophied and ischemic human hearts. Circulation, 88(3):864-875.

[11] Peters, N.S., del Monte, F., MacLeod, K.T., Green, C.R., Poole-Wilson, P.A., Severs, N.J., 1993b. Increased cardiac myocyte gap-junctional membrane early in renovascular hypertension. Am. J. Cardiol., 21:59A (Abstracts).

[12] Pimentel, R.C., Yamada, K.A., Klebr, A.G., Saffitz, J.E., 2002. Autocrine regulation of myocyte Cx43 expression by VEGF. Circ. Res., 90(6):671-677.

[13] Polontchouk, L., Haefliger, J.A., Ebelt, B., Schaefer, T., Stuhlmann, D., Mehlhorn, U., Kuhn-Regnier, F., de Vivie, E.R., Dhein, S., 2001. Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria. J. Am. Coll. Cardiol., 38(3):883-891.

[14] Polontchouk, L., Ebelt, B., Jackeis, M., Dhein, S., 2002. Chronic effect of endothelin 1 and angiotensin II on gap junctions and intercellular communication in cardiac cells. FASEB J., 16(1):87-89.

[15] Purcell, N.H., Tang, G., Yu, C., Mercurio, F., Di Donato, J.A., Lin, A., 2001. Activation of NF-kappaB is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes. Proc. Natl. Acad. Sci. USA, 98(12):6668-6673.

[16] Saffitz, J.E., Schuessler, R.B., Yamada, K.A., 1999. Mechanisms of remodeling of gap junction distributions and the development of anatomic substrates of arrhythmias. Cardiovasc. Res., 42(2):309-317.

[17] Severs, N.J., 1999. Cardiovascular disease. Novartis Found Symp., 219:188-211.

[18] Severs, N.J., Coppen, S.R., Dupont, E., Yeh, H.I., Ko, Y.S., Matsushita, T., 2004. Gap junction alterations in human cardiac disease. Cardio. Res., 62(2):368-377.

[19] Shyu, K.G., Chen, C.C., Wang, B.W., Kuan, P., 2001. Angiotensin II receptor antagonist blocks the expression of connexin43 induced by cyclical mechanical stretch in cultured neonatal rat cardiac myocytes. J. Mol. Cell. Cardiol., 33(4):691-698.

[20] Uzzaman, M., Honji, H., Takagishi, Y., Emad, L., Anthoy, I., Magee, A.I., Severs, N.J., Kodama, I., 2000. Remodelling of gap junctional coupling of rats with monocrotaline-induced pulmonary hypertension. Circ. Res., 86(8):871-878.

[21] Vakili, B.A., Okin, P.M., Devereux, R.B., 2001. Prognostic implications of left ventricular hypertrophy. Am. Heart J., 141(3):334-341.

[22] Yeh, H.I., Lee, P.Y., Su, C.H., Tian, T.Y., Ko, Y.S., Tsai, C.H., 2006. Reduced expression of endothelial connexins 43 and 37 in hypertensive rats is rectified after 7-day carvedilol treatment. Am. J. Hypertens., 19(2):129-135.

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