Several pathological conditions predict the use of glucocorticoids for the management of the inflammatory response; however, chronic or high dose glucocorticoid treatment is associated with ...hyperglycemia, hyperlipidemia, and insulin resistance and can be considered a risk factor for cardiovascular disease. Therefore, we investigated the mechanisms involved in the vascular responsiveness and inflammatory profile of mesenteric arteries of rats treated with high doses of glucocorticoids. Wistar rats were divided into a control (CO) group and a dexamethasone (DEX) group, that received dexamethasone for 7 days (2mg/kg/day, i.p.). Blood samples were used to assess the lipid profile and insulin tolerance. Vascular reactivity to Phenylephrine (Phe) and insulin, and O2•-production were evaluated. The intracellular insulin signaling pathway PI3K/AKT/eNOS and MAPK/ET-1 were investigated. Regarding the vascular inflammatory profile, TNF-α, IL-6, IL-1β and IL-18 were assessed. Dexamethasone-treated rats had decreased insulin tolerance test and endothelium-dependent vasodilation induced by insulin. eNOS inhibition caused vasoconstriction in the DEX group, which was abolished by the ET-A antagonist. Insulin-mediated relaxation in the DEX group was restored in the presence of the O2.- scavenger TIRON. Nevertheless, in the DEX group there was an increase in Phe-induced vasoconstriction. In addition, the intracellular insulin signaling pathway PI3K/AKT/eNOS was impaired, decreasing NO bioavailability. Regarding superoxide anion generation, there was an increase in the DEX group, and all measured proinflammatory cytokines were also augmented in the DEX group. In addition, the DEX-group presented an increase in low-density lipoprotein cholesterol (LDL-c) and total cholesterol (TC) and reduced high-density lipoprotein cholesterol (HDL-c) levels. In summary, treatment with high doses of dexamethasone promoted changes in insulin-induced vasodilation, through the reduction of NO bioavailability and an increase in vasoconstriction via ET-1 associated with generation of O2•- and proinflammatory cytokines.
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.
•Autonomic imbalance underlies hypertension in dexamethasone-treated rats.•Dexamethasone causes cardiac oxidative stress without ventricular dysfunction.•Dexamethasone-treated rats displayed greater cardiac fibrosis.•Dexamethasone-treated rats have higher incidence of arrhythmias.•Inhibition of NADPH oxidase prevents arrhythmias in dexamethasone-treated rats.
This study evaluated whether resistance training (RT) could prevent glucocorticoid-induced vascular changes. Wistar rats were divided into groups: control (CO), dexamethasone (DEX), and ...Dexamethasone+RT (DEX+RT). On the eighth week, dexamethasone was administered in the DEX and DEX+RT groups. Thereafter, the animals were sacrificed and blood samples were used to assess the lipid profile, glucose and insulin. Vascular reactivity to insulin and phenylephrine (Phe) were evaluated. The DEX+RT group presented an improvement in the lipid profile, fasting glucose, and insulin levels compared to the DEX group. In addition, vasodilation was reduced in the DEX group compared to the CO group, and was increased in the DEX+RT group. After inhibition of phosphatidylinositol 3-kinase, DEX group showed contraction, in which it was in the DEX + RT group. When nitric oxide synthase (NOS) participation was evaluated, the DEX group presented a contraction compared to the CO group, with no contractile effect in the DEX+RT group. Moreover, vasoconstriction caused by NOS inhibition was abolished by BQ123 (endothelin receptor antagonist). In respect Phe response, there was an increase in tension in the DEX group compared to the CO group, being reduced in the DEX+RT group. The results suggest that RT prevented damage to vascular reactivity.
Hypertension is a public health problem and increases the incidence of cardiovascular diseases.
To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of ...vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats.
Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP).
Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H.
One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.
Resistance exercise effects on cardiovascular parameters are not consistent.
The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in ...diabetic rats.
Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings.
A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group.
Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats.
ABSTRACT The aim of the study was to evaluate the acute resistance exercise on glucose metabolism in animals with insulin resistance. 30 Wistar rats were divided into three groups: control (CON), ...Dexamethasone Sedentary (DS) and dexamethasone + exercise (DE). Resistance exercise was conducted in the squat machine consisting of five sets, 10 repetitions, with intensity of 70% of 1RM. Concurrently, the DS and DE groups received daily intraperitoneal dexamethasone (4.0mg / kg). The body weight, glycemia and insulin sensitivity test were measured in all groups. One single resistance exercise session reduced blood glucose levels and improved insulin sensitivity. The DT group showed a lower area under the curve when compared to the DS group. The high intensity acute resistance exercise promoted a reduction of blood glucose levels and improved insulin sensitivity in rats with insulin resistance dexamethasone- induced.
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