Abstract

β2-Adrenoceptors Antiarrhythmic Effects in Wild Type Mice Fed a Cholesterol-Enriched Diet

Simone Correia Ternes, Leandro Eziquiel de Souza, Paula Lazara Cruz, Cristiano Teixeira Mostarda, Maria Cláudia Costa Irigoyen, Vitor Rossi de Almeida, André Luiz de Moura, Luciana Le Sueur Maluf, Daniela Ortolani, Daniel Araki Ribeiro, Isabel Cristina Céspedes and Regina Célia Spadari

The systematic intake of an unbalanced diet is an important risk factor for cardiovascular diseases, the leading cause of death in the entire world. Most of the studies address this issue using genetically manipulated mice. This study aims to investigate the effect of the intake of a cholesterol-enriched diet on cardiac and hemodynamic parameters in conscious wild type mice. Twenty male, three-month-old C57BL/6 mice were distributed in two groups: (CTL) control, with mice receiving standard commercial chow and (CHO) cholesterol group, with mice receiving a cholesterol-enriched diet during 15 days. Catheters were implanted in the carotid artery and jugular vein for blood pressure and heart rate recording and drugs administration. Electrodes were implanted for electrocardiogram recording and spectral analysis of heart rate variability. Glucose, cholesterol, and triglycerides were determined in blood samples and histopathological analysis of the aorta was performed. Serum cholesterol and glucose, mean arterial pressure and heart rate were higher in CHO than CTL mice. CHO mice also exhibited a predominance of sympathetic over parasympathetic tonus to the heart and higher responsiveness to the chronotropic effect of isoproterenol. Arrhythmic episodes, present only in the CHO mice, were canceled by metoprolol and exacerbated by ICI118,551. It is concluded that the intake of high cholesterol diet causes hypertension and heart rhythm irregularities. Because those effects are exacerbated by the blockade of the β2-adrenergic receptor and attenuated by the blockade of the β1-adrenergic receptor, data highlights a possible antiarrhythmic protective role played by β2-AR subtype.