Myocardial hypertrophy is prevented by farnesol through oxidative stress and ERK1/2 signaling pathways.

Farnesol is a sesquiterpene found in several plants, with multiple pharmacological activities. However, pharmacological actions of farnesol in the treatment of cardiac hypertrophy are not yet reported. This study aimed to investigate the effect and regulatory mechanisms of farnesol against isoproterenol-induced pathological cardiac hypertrophy. Male Wistar rats were treated for 8 days with isoproterenol (4.5 mg/kg; i. p.) and with farnesol (50 µM; i. p.). Hearts were subjected to evaluation of left ventricular developed pressure (LVDP), coronary pressure, electrocardiogram, histopathological analysis, reactive oxygen species (ROS) generation, antioxidant enzyme activity, and pro- and anti-apoptosis protein expression. The results showed that severe impairment of LVDP induced by cardiac hypertrophy was significantly prevented by farnesol treatment. Moreover, farnesol attenuated electrocardiographic changes that are characteristic of cardiac hypertrophy, as well as prevented the increase of fibrosis and migration of inflammatory cells in cardiac tissue. Additionally, farnesol treatment prevented the increase of cardiac ROS generation and restored the activity of endogenous antioxidant enzymes, such as SOD and catalase. It was also evidenced that farnesol decreased the ERK1/2, Bax and Caspase 3 activation, and an increase of AKT and Bcl-2 protein expression, which can be associated with the pathological cardiac remodeling and also with cardioprotection mediated by farnesol, respectively. These results suggest that farnesol is a novel therapeutic agent for amelioration of cardiac hypertrophy in rats.

Resistance training improves cardiovascular autonomic control and biochemical profile of rats exposed to Western diet in the perinatal period. / Treinamento resistido melhora controle autonômico cardiovascular e perfil bioquímico de ratos expostos a dieta ocidental no período perinatal.

INTRODUCTION AND OBJECTIVES: Consumption of a Western diet during the perinatal period is associated with development of cardiovascular disease. Resistance training (RT) has been used to treat cardiovascular disorders. The aim of this work was to assess the effect of RT on cardiometabolic disorders in rats exposed to a Western diet in the perinatal period. METHODS: Female Wistar rats were fed with control or Western diet during pregnancy and lactation. The pups were divided into three groups: Control (C), Western Diet Sedentary (WDS) and Western Diet + RT (WDRT). At 60 days of age, all animals started the RT protocol (five times a week for four weeks). At the end, blood pressure was recorded for analysis of heart rate variability and baroreflex sensitivity (BRS). Blood samples were collected for biochemical analysis. RESULTS: RT reduced blood pressure and vascular sympathetic modulation and increased BRS. There were improvements in biochemical profile, with reductions in fasting blood glucose, total cholesterol and low-density lipoprotein, and an increase in high-density lipoprotein. CONCLUSION: RT led to beneficial adaptations in the cardiovascular system, mediated by changes in the mechanisms of autonomic control and biochemical profile of animals exposed to a Western diet in the perinatal period.

Resistance exercise mediates remote ischemic preconditioning by limiting cardiac eNOS uncoupling.

BACKGROUND: Currently viewed as a complementary non-pharmacological intervention for preventing cardiac disorders, long-term aerobic training produces cardioprotection through remote ischemic preconditioning (RIPC) mechanisms. However, RIPC triggered by acute exercise remains poorly understood. Although resistance exercise (RE) has been highly recommended by several public health guidelines, there is no evidence showing that RE mediates RIPC. Hence, we investigated whether RE induces cardiac RIPC through nitric oxide synthase (NOS)-dependent mechanism. METHODS AND RESULTS: Acute RE at 40% of the maximal load augmented systemic nitrite levels, associated with increased cardiac eNOS phosphorylation, without affecting nNOS activity. Using an experimental model of myocardial infarction (MI) through ischemia-reperfusion (IR), RE fully prevented the loss of cardiac contractility and the extent of MI size compared to non-exercised (NE) rats. Moreover, RE mitigated aberrant ST-segment and reduced life-threatening arrhythmias induced by IR. Importantly, inhibition of NOS abolished the RE-mediated cardioprotection. After IR, NE rats showed increased cardiac eNOS activity, associated with reduced dimer/monomer ratio. Supporting the pivotal role of eNOS coupling during MI, non-exercised rats displayed a marked generation of reactive oxygen species (ROS) and oxidative-induced carbonylation of proteins, whereas RE prevented these responses. We validated our data demonstrating a restoration of physiological ROS levels in NE + IR cardiac sections treated with BH4, a cofactor oxidatively depleted during eNOS uncoupling, while cardiac ROS generation from exercised rats remained unchanged, suggesting no physiological needs of supplemental eNOS cofactors. CONCLUSION: Together, our findings strongly indicate that RE mediates RIPC by limiting eNOS uncoupling and mitigates myocardial IR injury.