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Long‑term treatment of spontaneously hypertensive rats with losartan and molecular basis of modulating Ito of ventricular myocytes.
Mol Med Rep. 2014 May; 9(5):1959-67.MM

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 lo-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.

Authors+Show 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.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.Department of Cardiology, The General Hospital of Jinan Military Region, Jinan, Shandong 250031, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24584699

Citation

Zhang, Hongming, et al. "Long‑term Treatment of Spontaneously Hypertensive Rats With Losartan and Molecular Basis of Modulating Ito of Ventricular Myocytes." Molecular Medicine Reports, vol. 9, no. 5, 2014, pp. 1959-67.
Zhang H, Wu S, Huang C, et al. Long‑term treatment of spontaneously hypertensive rats with losartan and molecular basis of modulating Ito of ventricular myocytes. Mol Med Rep. 2014;9(5):1959-67.
Zhang, H., Wu, S., Huang, C., & Li, X. (2014). Long‑term treatment of spontaneously hypertensive rats with losartan and molecular basis of modulating Ito of ventricular myocytes. Molecular Medicine Reports, 9(5), 1959-67. https://doi.org/10.3892/mmr.2014.2001
Zhang H, et al. Long‑term Treatment of Spontaneously Hypertensive Rats With Losartan and Molecular Basis of Modulating Ito of Ventricular Myocytes. Mol Med Rep. 2014;9(5):1959-67. PubMed PMID: 24584699.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long‑term treatment of spontaneously hypertensive rats with losartan and molecular basis of modulating Ito of ventricular myocytes. AU - Zhang,Hongming, AU - Wu,Songlin, AU - Huang,Congxing, AU - Li,Xiaoyan, Y1 - 2014/02/28/ PY - 2013/06/24/received PY - 2014/02/07/accepted PY - 2014/3/4/entrez PY - 2014/3/4/pubmed PY - 2014/11/19/medline SP - 1959 EP - 67 JF - Molecular medicine reports JO - Mol Med Rep VL - 9 IS - 5 N2 - 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 lo-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. SN - 1791-3004 UR - https://www.unboundmedicine.com/medline/citation/24584699/Long‑term_treatment_of_spontaneously_hypertensive_rats_with_losartan_and_molecular_basis_of_modulating_Ito_of_ventricular_myocytes_ DB - PRIME DP - Unbound Medicine ER -