ABSTRACT
Studies have shown a cardioprotective role of thyroid hormones (THs) in cardiac remodeling after acute myocardial infarction (MI). However, there is no data in the literature examining the influence of TH administration on the aortic tissue in an animal model of MI. This study aimed to evaluate the effects of thyroid hormones on the aorta after MI. Male Wistar rats were divided into a sham group (SHAM), infarcted group (AMI), sham+TH (SHAMT) and AMI+TH (AMIT). After MI, the animals received T3 and T4 (2 and 8µg/100g/day, respectively) by oral gavage for 12 days. Later, the animals underwent echocardiography and euthanasia and the aorta was collected for molecular and biochemical analysis. T3 and T4 administration increased the expression of the pro-angiogenic proteins vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1α (HIF-1α) in the aorta of AMIT rats when compared with AMI. With respect to TH receptors, AMI rats presented a decrease in TRß levels, which was prevented by the hormonal administration. In AMIT rats, both TRα and TRß levels were increased when compared with the AMI group. Reactive oxygen species levels and NADPH oxidase activity were decreased in both treated groups when compared with the non-treated animals. TH administration after MI may improve angiogenic signaling in the aorta as well as the responsiveness of this vessel to T3 and T4. These positive effects in the aorta may result in additional protection for the cardiovascular system in the context of cardiac ischaemic injury.
Subject(s)
Aorta/drug effects , Aorta/metabolism , Myocardial Infarction/pathology , Thyroid Hormones/pharmacology , Angiotensin I/metabolism , Animals , Gene Expression Regulation/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Male , Myocardial Infarction/metabolism , NADPH Oxidases/metabolism , Oxidative Stress/drug effects , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Receptors, Thyroid Hormone/metabolism , Vascular Endothelial Growth Factor A/metabolism , Xanthine Oxidase/metabolismABSTRACT
Apoptosis is a key process associated with pathological cardiac remodelling in early-phase post-myocardial infarction. In this context, several studies have demonstrated an anti-apoptotic effect of thyroid hormones (TH). The aim of this study was to evaluate the effects of TH on the expression of proteins associated with the apoptotic process 14 days after infarction. Male Wistar rats (300-350 g) (n = 8/group) were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT) and infarcted + TH (AMIT). For 12 days, the animals received T3 and T4 [2 and 8 µg/(100 g day)] by gavage. After this, the rats were submitted to haemodynamic and echocardiographic analysis, and then were sacrificed and the heart tissue was collected for molecular analysis. Statistical analyses included two-way ANOVA with Student-Newman-Keuls post test. Ethics Committee number: 23262. TH administration prevented the loss of ventricular wall thickness and improved cardiac function in the infarcted rats 14 days after the injury. AMI rats presented an increase in the pro-apoptotic proteins p53 and JNK. The hormonal treatment prevented this increase in AMIT rats. In addition, TH administration decreased the Bax:Bcl-2 ratio in the infarcted rats. TH administration improved cardiac functional parameters, and decreased the expression of pro-apoptotic proteins 14 days after myocardial infarction.
Subject(s)
Apoptosis Regulatory Proteins/metabolism , Cardiotonic Agents/administration & dosage , Myocardial Infarction/drug therapy , Myocardium/metabolism , Thyroxine/administration & dosage , Triiodothyronine/administration & dosage , Animals , Apoptosis Regulatory Proteins/genetics , Cardiotonic Agents/pharmacokinetics , Drug Evaluation, Preclinical , Gene Expression , Lipid Peroxidation , Male , Myocardial Infarction/metabolism , Myocardium/pathology , Oxidation-Reduction , Oxidative Stress , Rats, Wistar , Reactive Oxygen Species/metabolism , Thyroxine/pharmacokinetics , Triiodothyronine/pharmacokinetics , Ventricular Pressure/drug effectsABSTRACT
We tested the influence of estrogen on coronary resistance regulation by modulating nitric oxide (NO) and hydrogen peroxide (H2O2) levels in female rats. For this, estrogen levels were manipulated and the hearts were immediately excised and perfused at a constant flow using a Langendorff's apparatus. Higher estrogen levels were associated with a lower coronary resistance, increased nitric oxide bioavailability, and higher levels of H2O2. When oxide nitric synthase blockade by L-NAME was performed, no significant changes were found in coronary resistance of ovariectomized rats. Additionally, we found an inverse association between NO levels and catalase activity. Taken together, our data suggest that, in the absence of estrogen influence and, therefore, reduced NO bioavailability, coronary resistance regulation seems to be more dependent on the H2O2 that is maintained at low levels by increased catalase activity.
