Long‑term treatment of spontaneously hypertensive rats with losartan and molecular basis of modulating Ito of ventricular myocytes

Zhang,Hongming; Wu,Songlin; Huang,Congxing; Li,Xiaoyan

doi:10.3892/mmr.2014.2001

May-2014 Volume 9 Issue 5

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May-2014 Volume 9 Issue 5

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Article

Long‑term treatment of spontaneously hypertensive rats with losartan and molecular basis of modulating Ito of ventricular myocytes

Authors:
- Hongming Zhang
- Songlin Wu
- Congxing Huang
- Xiaoyan Li
View Affiliations / Copyright

Affiliations: Department of Cardiology, The General Hospital of Jinan Military Region, Jinan, Shandong 250031, P.R. China, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Pages: 1959-1967
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Published online on: February 28, 2014

https://doi.org/10.3892/mmr.2014.2001
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Abstract

The present study aimed to determine the effect of chronic treatment with losartan on transient outward potassium current (Ito) and the expression levels of potassium voltage‑gated channel subfamily D members 2 and 3 (Kv4.2 and 3) and voltage‑gated potassium channel‑interacting protein 2 (KChIP2) in rats. Spontaneously hypertensive (SH) rats and Wistar‑Kyoto (WKY) rats were used in the study. The rats were divided into los‑SH and SH groups and los‑WKY and WKY groups, respectively. Ito was recorded and expression levels of Kv4.2, Kv4.3 and KChIP2 were measured by western blot analysis and quantitative polymerase chain reaction. Ito current density was smaller in SH compared with WKY, los‑WKY and los‑SH groups (P<0.01). Inactivation time constant of myocytes was larger in SH compared with WKY, los‑WKY and los‑SH groups (P<0.01). The mean levels of mRNA and protein of Kv4.2 and Kv4.3 were significantly lower in the SH compared with WKY, los‑WKY and los‑SH groups in vivo and in vitro (P<0.01). The Pearson statistical test showed no correlation between the expression levels of Kv4.2, Kv4.3, KChIP2 and the changes in blood pressure in the losartan treatment group. In conclusion, chronic blockade of angiotensin II type 1 receptors with losartan reversed SH rats' electrical remodeling and shortened action potential duration, which was associated with an increase in Ito density as the expression levels of Kv4.2, Kv4.3 increased and the expression levels of KChIP2 decreased. However, the expression levels of Kv4.2, Kv4.3 and KChIP2 were not correlated with the change in blood pressure in the losartan treatment group. Losartan may decrease the inactivation time by increasing the expression of KChIP2.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Long‑term treatment of spontaneously hypertensive rats with losartan and molecular basis of modulating Ito of ventricular myocytes

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