Sexual dimorphism in autonomic changes and in the renin-angiotensin system in the hearts of mice subjected to thyroid hormone-induced cardiac hypertrophy

Abstract

New Findings: What is the central question of this study? Based on the relevance of the renin-angiotensin system and the controversy regarding the role of the sympathetic nervous system in thyroid hormone-related cardiac hypertrophy, the present study sought to establish whether there is a gender difference in activation of these systems and the degree of cardiac hypertrophy in mice. What is the main finding and its importance? Triiodothyronine increased sympathetic modulation and induced higher levels of cardiac angiotensin II in male than in female mice. This could explain the greater degree of cardiac hypertrophy induced by thyroid hormone found in the male mice. Based on the relevance of the renin-angiotensin system and the ongoing controversy regarding the role of the sympathetic nervous system in thyroid hormone-induced cardiac hypertrophy, the aim of the present study was to establish whether the putative difference in the degree of cardiac hypertrophy exhibited by males and females might be related to differences in the sympathetic-vagal balance and/or in the cardiac renin-angiotensin system in mice of different genders. Male and female mice (n = 117) were given 0.1 mg kg-1 of triiodothyronine or normal saline each day for 10 days consecutively. At the end of that period, study of the heart rate variability, spectral analysis and histopathological examination were performed to assess the sympathetic-vagal balance and the diameter of cardiomyocytes. The cardiac levels of angiotensin I and II were also measured. Treatment with triiodothyronine induced a greater degree of cardiac hypertrophy in male (~73%) than in female mice (~42%). This difference was attributed to greater modulation of the sympathetic nervous system and higher levels of angiotensin I and II in male than in female mice. Our data indicate that thyroid hormone-induced cardiac hypertrophy was more intense in male mice due to the synergic effect of the sympathetic nervous system and the cardiac renin-angiotensin system. © 2014 The Physiological Society.