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Chronic enalapril treatment increases transient outward potassium current in cardiomyocytes isolated from right ventricle of spontaneously hypertensive rats

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Abstract

It has been well established that chronic pressure overload resulting from hypertension leads to ventricular hypertrophy and electrophysiological remodeling. The transient outward potassium current (I to) reduction described in hypertensive animals delays ventricular repolarization, leading to complex ventricular arrhythmias and sudden death. Antihypertensive drugs, as angiotensin-converting enzyme inhibitors (ACEi), can restore I to and reduce the incidence of arrhythmic events. The purpose of this study was to evaluate the differential effects of long-term treatment with ACEi or direct-acting smooth muscle relaxant on the I to of left and right ventricle myocytes of spontaneously hypertensive rats (SHR). Animals were divided into four groups: normotensive Wistar-Kyoto rats (WKY), hypertensive (SHR), SHR treated for 6 weeks with enalapril 10 mg/kg/day (SHRE), or hydralazine 20 mg/kg/day (SHRH). Systolic blood pressure (SBP) and hypertrophy index (heart weight/body weight (HW/BW)) were determined at the end of treatment period. Cell membrane capacitance (C m) and I to were assessed in cardiomyocytes isolated from left and right ventricles. The SHR exhibited significantly increased SBP and HW/BW when compared to the WKY. The treated groups, SHRE and SHRH, restored normal SBP but not HW/BW. The SHR group exhibited a diminished I to in the left but not the right ventricle. Both the treated groups restored I to in the left ventricle. However, in the right ventricle, only enalapril treatment modified I to. The SHRE group exhibited a significant increase in I to compared to all the other groups. These findings suggest that enalapril may increase I to by a pressure overload independent mechanism.

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Acknowledgements

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ). JHMN and JGM are research fellows from the CNPq. LFRJ and ACAC received fellowships from the CNPq.

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Authors and Affiliations

  1. Institute of Biophysics Carlos Chagas Filho, Laboratory of Cardiac Electrophysiology Antonio Paes de Carvalho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373 - CCS Bloco G - Ilha do Fundao, 21, Rio de Janeiro, RJ, 941-902, Brazil

    Luiz Fernando Rodrigues Junior, Ana Carolina de Azevedo Carvalho & José Hamilton Matheus Nascimento

  2. Department of Physiological Sciences, Laboratory of Cardiovascular Biophysics, Federal University of State of Rio de Janeiro, Rio de Janeiro, Brazil

    Luiz Fernando Rodrigues Junior

  3. Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Brazil

    Enildo Broetto Pimentel & José Geraldo Mill

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  1. Luiz Fernando Rodrigues Junior
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  2. Ana Carolina de Azevedo Carvalho
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  3. Enildo Broetto Pimentel
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  4. José Geraldo Mill
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  5. José Hamilton Matheus Nascimento
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Correspondence to José Hamilton Matheus Nascimento.

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The experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85-23, revised 1996), and approved by the Institutional Animal Care and Use Committee (IBCCF-010).

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Rodrigues Junior, L.F., de Azevedo Carvalho, A.C., Pimentel, E.B. et al. Chronic enalapril treatment increases transient outward potassium current in cardiomyocytes isolated from right ventricle of spontaneously hypertensive rats. Naunyn-Schmiedeberg's Arch Pharmacol 390, 225–234 (2017). https://doi.org/10.1007/s00210-016-1322-7

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