Potential role of AT2R on the cardiac mitochondrial metabolism in the hyperthyroidism condition (1159.8)

Abstract

Thyroid hormone (TH) is known to influence the mitochondrial metabolism. Recently, it has been proposed that the intracellular renin angiotensin system (iRAS) seems to be activated by high levels of (TH). However, the contribution of AT2R in the regulation of cardiac mitochondrial metabolism or the possible effect of TH on this event was not elucidated yet. We investigated the potential role of AT2R on the cardiac mitochondrial metabolism and the possible influence of the hyperthyroidism on this process. Four groups of mice were used: wild‐type (WT), WT treated with TH (0.7 µg/Kg BW/day, i.p.) for 14 days, knockout (KO AT2R‐/y) mice and KO AT2R‐/y mice treated with TH. Cardiac mitochondria were isolated and the oxygen consumption was assessed by oxymetry. The H2O2 production was also analyzed. The determination of maximal oxygen uptake was determined by indirect calorimetry open circuit. Data were analyzed by two‐way ANOVA. The KO mice presented a reduction in all parameters analyzed: states 2, 3, 4 and respiratory control ratio in relation to control. The TH‐treated WT did not present changes on H2O2 production. However, H2O2 production was higher on KO mice treated with TH. Indeed, the calorimetry showed a decrease (17%) on basal metabolic rate of on KO mice. Taken together, our data show that AT2R may be involved in the control of cardiac mitochondrial metabolism and influence the effect of hyperthyroidism in this parameter.Grant Funding Source: Supported by CNPq/CAPES and FAPESP