RESUMO
AIM: To investigate the effect of acute treatment with the anabolic steroid (AS) nandrolone decanoate in mitochondrial homeostasis and JAK-STAT3 signaling during the progression of cardiac ischemia/reperfusion injury (IR). METHODS: Male Wistar rats (2 months old) were randomly allocated into four experimental groups: Control (CTRL), IR, AS, and AS + AG490. All animals were euthanized 3 days after a single intramuscular injection of nandrolone at 10 mg/kg (AS and AS + AG490 groups) or vehicle (CTRL and IR groups). Baseline mRNA expression of antioxidant enzymes superoxide dismutase (SOD) 1 and 2, glutathione peroxidase, catalase, and myosin heavy chain (MHC) α and ß were compared between CTRL and AS groups. Isolated hearts were submitted to ex vivo ischemia and reperfusion, except for hearts from the CTRL group. Before the IR protocol, the JAK-STAT3 inhibitor AG490 was perfused in hearts from the AS + AG490 group. Heart samples were collected during reperfusion to investigate the effects on mitochondrial function. Results Antioxidant enzyme mRNA expression was unaffected, whereas the AS group exhibited decreased ß- MHC/α-MHC ratio versus the CTRL group. Compared to the IR group, the AS group exhibited better recovery of post-ischemic left ventricular (LV) end-diastolic pressure and LV-developed pressure levels, while infarct size significantly decreased. Furthermore, mitochondrial production, transmembrane potential, and swelling were improved, whereas ROS formation was decreased versus the IR group. These effects were prevented by the perfusion of JAK-STAT3 inhibitor AG490. CONCLUSION: These findings suggest that acute nandrolone treatment can provide cardioprotection by recruiting the JAK-STAT3 signaling pathway and mitochondrial preservation.
Assuntos
Traumatismo por Reperfusão Miocárdica , Nandrolona , Ratos , Animais , Masculino , Antioxidantes , Ratos Wistar , Mitocôndrias/metabolismo , RNA MensageiroRESUMO
PURPOSE: In the present study, the therapeutic efficacy of a selective BKCa channel opener (compound X) in the treatment of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) was investigated. METHODS: PAH was induced in male Wistar rats by a single injection of MCT. After two weeks, the MCT-treated group was divided into two groups that were either treated with compound X or vehicle. Compound X was administered daily at 28 mg/kg. Electrocardiographic, echocardiographic, and haemodynamic analyses were performed; ex vivo evaluations of pulmonary artery reactivity, right ventricle (RV) and lung histology as well as expression levels of α and ß myosin heavy chain, brain natriuretic peptide, and cytokines (TNFα and IL10) in heart tissue were performed. RESULTS: Pulmonary artery rings of the PAH group showed a lower vasodilatation response to acetylcholine, suggesting endothelial dysfunction. Compound X promoted strong vasodilation in pulmonary artery rings of both control and MCT-induced PAH rats. The untreated hypertensive rats presented remodelling of pulmonary arterioles associated with increased resistance to pulmonary flow; increased systolic pressure, hypertrophy and fibrosis of the RV; prolongation of the QT and Tpeak-Tend intervals (evaluated during electrocardiogram); increased lung and liver weights; and autonomic imbalance with predominance of sympathetic activity. On the other hand, treatment with compound X reduced pulmonary vascular remodelling, pulmonary flow resistance and RV hypertrophy and afterload. CONCLUSION: The use of a selective and potent opener to activate the BKCa channels promoted improvement of haemodynamic parameters and consequent prevention of RV maladaptive remodelling in rats with MCT-induced PAH.