title: Chronic enalapril treatment increases transient outward potassium current in cardiomyocytes isolated from right ventricle of spontaneously hypertensive rats.
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 (Ito) 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 Itoand 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 Itoof 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 (Cm) and Itowere 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 Itoin the left but not the right ventricle. Both the treated groups restored Itoin the left ventricle. However, in the right ventricle, only enalapril treatment modified Ito. The SHRE group exhibited a significant increase in Itocompared to all the other groups. These findings suggest that enalapril may increase Itoby a pressure overload independent mechanism.
authors.affiliation: 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.|Department of Physiological Sciences, Laboratory of Cardiovascular Biophysics, Federal University of State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Rodrigues Junior
authors.affiliation: 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.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Azevedo Carvalho
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Brazil.
authors.forename: Enildo Broetto
authors.initials: EB
authors.lastname: Pimentel
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Brazil.
authors.forename: José Geraldo
authors.initials: JG
authors.lastname: Mill
authors.affiliation: 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. jhmn@biof.ufrj.br.
authors.forename: José Hamilton Matheus
authors.initials: JH
authors.lastname: Nascimento
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000503:physiopathology; D004195:Disease Models, Animal; D025802:Electric Capacitance; D004656:Enalapril / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015221:Potassium Channels; D014665:Vasodilator Agents; D006830:Hydralazine; D004656:Enalapril; D011188:Potassium
keywords: Angiotensin-converting enzyme inhibitors; Enalapril; Hypertension; Hypertrophy; SHR; Transient outward potassium current