Alterações cardiovasculares induzidas por fenilefrina em animais Knockout para o receptor Mas

Abstract

Sympathetic activation is modulated by adrenergic receptors and stimulation of these receptors by excessive circulating catecholamines causes cardiac remodeling, with consequent deterioration of myocardial function. It is known that the Renin-Angiotensin system has an important role in this process, being the Ang-(1-7)/Mas receptor axis the main route to cardioprotection and to induce cardio counterregulatory responses to Ang II/AT 1 receptor axis. The development of animals with genetic deletion of the receptor Mas (Mas-Ko), has brought great progress in understanding the functions and cellular mechanisms activated by Ang- (1-7) / Mas axis. The present study aimed to identify the cardiovascular abnormalities induced by the stressor phenylephrine and to compare the response of animals Mas-Ko with the responses of wild-type mice (WT), in order to better understanding the mechanism of the Ang - (1-7) / receptor Mas axis. WT and KO animals were treated with phenylephrine for 7 and 14 days and their respective control with saline solution. Our results showed that WT mice treated for 7 days with phenylephrine presented responses consistent with the expected response to treatment with phenylephrin: (i) hypertrophy of the heart and cardiomyocytes, (ii) increased production of reactive oxygen species (ROS), (ii) change in expression of antioxidant enzymes, (iii) increased amplitude of the Ca2 + transient and (iv) increased heart ejection fraction. Prolonged treatment with phenylephrine led to (v) a decrease in Ca2+ transient amplitude and (vi) a decrease in ejection fraction. On the other hand, treatment of KO mice with phenylephrine for 7 days showed distinct response patterns: (i) cardiomyocytes were not hypertrophied, (ii) ROS production and expression of antioxidant enzymes were not significantly altered. Also, prolonged treatment of KO mice with phenylephrine, was not related to changes in Ca2+ transient amplitude or altered ejection fraction. These data suggest that Mas-Ko mice respond with less harmful alterations when treated with phenylephrine as compared to wild type animals.