Dexamethasone is the most clinically used glucocorticoid with an established role in the treatment of a wide spectrum of inflammatory-related diseases. While the therapeutic actions are well known, dexamethasone treatment causes a number of cardiovascular side effects, which are complex, frequent and, in some cases, clinically unnoticeable. Here, we investigated whether a therapeutic regimen of dexamethasone affects cardiac arrhythmogenesis, focusing on the contribution of Nox-derived reactive oxygen species (ROS). Male Wistar rats were treated with dexamethasone (2 mg/kg, i.p.) for 7 days. Afterward, hemodynamic measurements, autonomic modulation, left ventricular function, cardiac fibrosis, reactive oxygen species (ROS) generation, Nox protein expression, superoxide dismutase (SOD) and catalase activities, and arrhythmias incidence were evaluated. Here, we show that dexamethasone increases blood pressure, associated with enhanced cardiac and vascular sympathetic modulation. Moreover, a marked increase in the cardiac ROS generation was observed, whereas the enhanced SOD activity did not prevent the higher levels of lipid peroxidation in the dexamethasone group. On the other hand, increased cardiac Nox 4 expression and hydrogen peroxide decomposition rate was observed in dexamethasone-treated rats, while Nox 2 remained unchanged. Interestingly, although preserved ventricular contractility and β-adrenergic responsiveness, we found that dexamethasone-treated rats displayed greater interstitial and perivascular fibrosis than control. Surprisingly, despite the absence of arrhythmias at basal condition, we demonstrated, by in vivo and ex vivo approaches, that dexamethasone-treated rats are more susceptible to develop harmful forms of ventricular arrhythmias when challenged with pharmacological drugs or burst pacing-induced arrhythmias. Notably, concomitant treatment with apocynin, an inhibitor of NADPH oxidase, prevented these ectopic ventricular events. Together, our results reveal that hearts become arrhythmogenic during dexamethasone treatment, uncovering the pivotal role of ROS-generating NADPH oxidases for arrhythmias vulnerability.

The aim of this study was to evaluate the vascular effects and participation of nitric oxide (NO) after a period of resistance training (RT). One group was submitted to RT (Ex). Control animals (SED) were fictitious trained (no exercise). After 8 weeks, mesenteric artery was removed and divided, one part was sliced in rings for vascular reactivity analysis (Acetilcholine (ACh): 10‐9 ‐ 10‐4 M; Nω‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME): 100µM; Phenylephrine (Phe): 10‐6 M) and the other half was probed with DAF‐FM dye to evaluation of NO bioavailability. Other animals were used to verify the nitric oxide synthases (NOS) expression using western blot technique. RT was able to increase percentage of ACh‐induced relaxation of mesenteric arterial rings (pD2: SED 6.2 ± 0.1 vs Ex 7.1 ± 0.1) and addition of L‐NAME abolished this effect (SED 52.0 ± 3.2% vs Ex 35.8 ± 3.7%). Moreover, RT reduced the level of tension in mesenteric rings with Phe‐induced contraction (SED 0.39 ± 0.06 vs Ex 0.20 ± 0.05) and addition of L‐NAME abolished this effect (SED 0.65 ± 0.05 vs Ex 0.88 ± 0.07). RT also increased the bioavailability of NO in both, basal (SED 0.99 ± 0.1 vs Ex 2.22 ± 0.16) and stimulated with ACh 10‐7 (SED 2.32 ± 0.16 vs 2.95 ± 0.2). In addition, RT increased eNOS (SED 0.21 ± 0.03 vs Ex 0.71 ± 0.07) and nNOS expression (SED 0.28 ± 0.06 vs Ex 0.76 vs 0.21). In conclusion, RT were able to promote endothelial adjustments, probably mediated by increased NO synthases.

The aim was evaluate if the alterations promoted by the insertion of a western diet during the perinatal period can be transgenerational. 4 female rats mated in the ratio 2:1. After pregnancy confirmation, a western on control diet was offered until the weaning of the pups. Pups of both groups were accompanied until complete 90 days, and then were placed to mate. After pregnancy confirmation, all rats were fed with a standard rodent diet. After weaning, rats were divided in 2 groups: second‐generation control offspring (2ºCO) and second‐generation western offspring (2ºWO), both fed with the same standard diet. Offspring body weight (BW) was measured weakly until the 90th day, dietary intake (DI) and calorie consumption (CC) was accompanied during a period of 10 days between the 30th and 40th day (young stage ‐YS) and the 60th and 70th day (adult stage ‐ AS). Offspring fasting glucose was evaluated with 30, 60 and 90 days. 2ºWO pups born with increased BW (2ºCO 5.41 ± 0.08 vs 2ºWO 6.82 ± 0.11) and maintained higher until 90th day(2ºCO 222 ± 5.11 vs 2ºWO 277 ± 4.6). In addition, 2ºWO pups had increased DI and CC in both periods, YS (DI: 2ºCO 121.3 ± 2.75 vs 2ºWO 132.6 ± 3.12) ‐ (CC: 2ºCO 552.14 ± 12.48 vs 2ºWO 603.42 ± 8.24) and AS (DI: 2ºCO 202.1 ± 6.42 vs 2ºWO 220 ± 2.64) ‐ (CC: 2ºCO 641.01 ± 21.11 vs 2ºWO 700.38 ± 14.11). In relation to fasting glucose, no change was observed in any of the periods (30 days: 2ºCO 84.83 ± 2.01 vs 2ºWO 89.5 ± 1.87; 60 days: 2ºCO 87.83 ± 3.88 vs 2ºWO 82.67 ± 2.60; 90 days: 2ºCO 93.83 ± 2.54 vs 2ºWO 82.66 ± 1.87). In conclusion, these findings suggests that dietary patterns influence directly the feeding behavior of future generations.

The aim was to evaluate the effects of low intensity resistance training (RT) on blood pressure, cardiovascular autonomic balance and vascular reactivity. One group of animals were submitted to RT. Control animals (CO) were fictitious trained (no exercise). After 8 weeks of RT or fictitious exercise, blood pressure and pulse interval were recorded and mesenteric artery was removed and sliced in rings for vascular reactivity analysis (Acetilcholine (ACh): 10‐9 ‐ 10‐4 M; Nω‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME): 100µM). The variabilities of pulse interval, blood pressure and spontaneous baroreflex sensitivity (BRS) were analyzed. RT animals showed a reduction in mean arterial pressure (CO 117.04 ± 2.68 vs RT 105.5 ± 4.28), diastolic arterial pressure (CO 107.71 ± 2.95 vs RT 97 ± 3.42) and heart rate (CO 395 ± 7.1 vs RT 344 ± 13.25). In addition, it was seen in trained animals an increase in cardiac vagal modulation (LF/HF: CO 0.35 ± 0.08 vs RT 0.14 ± 0.03), BRS (CO 0.77 ± 0.01 vs RT 1.05 ± 0.1) and percentage of ACh‐induced relaxation of mesenteric arterial rings (pD2: CO 6.2 ± 0.1 vs RT 7.1 ± 0.1) and addition of L‐NAME reduced the ACh‐induced relaxation (CO 52.0 ± 3.2% vs RT 35.8 ± 3.7%). In conclusion, we observed that low intensity RT was able to promote beneficial cardiovascular adaptations mediated by central and peripheral adjustments.Grant Funding Source: Supported by CNPq Foundation (Brazil)

An adequate nutritional support is important to ensure a normal development of the fetuses. Changes in the nutritional support during gestation may lead to transitory or permanent structural and functional changes of several organs of the offspring. We aimed to investigate the impact of a high fat diet during the gestation on cardiovascular and autonomic nervous systems (ANS) in the offspring of rats. High fat diet was given from day 1 of gestation until weaning of puppies. Sixty‐day‐old offspring from High Fat Diet dams (HFDD, n= 6) or Normal Diet dams (NDD, n= 6) had femoral arteries surgically assessed for the measurements of heart rate (HR), mean (MAP), systolic (SAP) and diastolic arterial pressure (DAP), and spontaneous baroreflex sensitivity (BRS). To investigate the balance of ANS, we established the high (HF) and low frequency (LF) bands of pulse interval (PI) and LF band of SAP spectrum. HFDD had increased MAP (135 ± 2vs 103± 1 mmHg, p<0.05), SAP (160 ± 3 vs 128 ± 4 mmHg, p<0.05), DAP (111 ± 2vs 91 ± 2 mmHg, p<0.05) and HR (417 ± 23 vs 352 ± 8 bpm, p<0.05) when compared to NDD. After spectral analysis of PI and SAP, LF band of SAP spectrum (6.19 ± 0.84 vs 2.29 ± 0.56 mmHg2, p<0.05) and LF/HF ratio of PI (0.71 ± 0.22 vs 0.14 ± 0.016 p<0.05) was higher in HFDD under spontaneous condition. These findings suggest that high fat diet during pregnancy and lactation leads to autonomic misbalance and hypertension in adult offspring rats.