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

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2017-03, Vol.390 (3), p.225-234
• Main Authors: Rodrigues Junior, Luiz Fernando, de Azevedo Carvalho, Ana Carolina, Pimentel, Enildo Broetto, Mill, José Geraldo, Nascimento, José Hamilton Matheus
• Format: Article
• Language: English
• Subjects: Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Antihypertensive Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Blood Pressure - drug effects; Cardiomegaly - physiopathology; Disease Models, Animal; Electric Capacitance; Enalapril - pharmacology; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Heart Ventricles - physiopathology; Hydralazine - pharmacology; Hypertension - drug therapy; Hypertension - metabolism; Hypertension - physiopathology; Male; Membrane Potentials; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Neurosciences; Original Article; Pharmacology/Toxicology; Potassium - metabolism; Potassium Channels - drug effects; Potassium Channels - metabolism; Rats, Inbred SHR; Rats, Inbred WKY; Time Factors; Vasodilator Agents - pharmacology; Ventricular Function, Left - drug effects; Ventricular Function, Right - drug effects
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-016-1322-7

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.