Exercise attenuates dexamethasone-induced hypertension through an improvement of baroreflex activity independently of the renin-angiotensin system

Abstract

Dexamethasone-induced hypertension may be caused by baroreflex alterations or renin-angiotensin system (RAS) exacerbation. Aerobic training has been recommended for hypertension treatment, but the mechanisms responsible for reduction of arterial pressure (AP) in dexamethasone (DEX) treated rats are still inconclusive.This study evaluated whether mechanisms responsible for training-induced attenuation of hypertension involve changes in autonomic nervous system and in RAS components. Rats underwent aerobic training protocol on treadmill or were kept sedentary for 8 weeks. Additionally, animals were treated with DEX during the last 10 days of exercise. Body weight (BW), AP and baroreflex activity were analyzed. Tibialis anterior (TA), soleus (SOL) and left ventricle (LV) were collected for evaluation of RAS components gene expression and protein levels. Dexamethasone decreased BW (20%), caused TA atrophy (16%) and increased systolic AP (SAP, 16%) as well as decreased baroreflex activity. Training attenuated SAP increase and improved baroreflex activity, although it did not prevent DEX-induced BW reduction and muscle atrophy. Neither DEX nor training caused expressive changes in RAS components. In conclusion, exercise training was effective in attenuating hypertension induced by DEX and this response may be mediated by a better autonomic balance through an improvement of baroreflex activity rather than changes in RAS components.

Dexamethasone and Training-Induced Cardiac Remodeling Improve Cardiac Function and Arterial Pressure in Spontaneously Hypertensive Rats

“…30 Although DEX is widely used to treat inflammation, 3 allergies, 4 vomiting and nausea 31 and cancer, 32 some side-effects are well described in normotensive rats, even after different doses, for instance, body weight reduction, muscle atrophy, peripheral insulin resistance, skeletal muscle microcirculation rarefaction and hypertension. [5][6][7][8][9][33][34][35] In agreement with previous results, in the present study, DEX treatment induced a significant reduction of SHR body weight. Also, adrenal gland weight was reduced, which confirms the effectiveness of the DEX treatment.…”

“…Although DEX is widely used to treat inflammation, 3 allergies, 4 vomiting and nausea 31 and cancer, 32 some side-effects are well described in normotensive rats, even after different doses, for instance, body weight reduction, muscle atrophy, peripheral insulin resistance, skeletal muscle microcirculation rarefaction and hypertension. 5 -9,33 -35…”

“…In addition, training was not able to attenuate these responses, as already shown in normotensive rats. [6][7][8]20,33 Reduction of body weight after DEX treatment could be a consequence of several factors, such as muscle atrophy and/or food intake reduction, 5 but the exact mechanism of body weight reduction was not the focus of this work.…”

“…1,2 Although dexamethasone (DEX) has a widespread use for inflammation and allergies, 3,4 there are growing evidence that it induces several side effects, like muscle atrophy, hyperglycemia, baroreflex alterations, autonomic imbalance to the heart, as well as hypertension and cardiac remodeling in normotensive animals. [5][6][7][8][9][10][11] In contrast, pre-treatment with DEX was able to decrease area of infarction and reduce apoptosis of cardiomyocytes in animals that had their anterior descending coronary occluded, due to an activation of anti-apoptotic protein Bcl-xL transcription. 12 In agreement, cardiomyocyte cells treated with corticosteroids showed reduced doxorubicininduced apoptotic response due to an increase in Bcl-xL.…”

“…7 Also, training improves baroreflex activity in DEX-induced hypertensive animals. 8 Some studies have demonstrated that training may attenuate cardiac remodeling in old SHR rats 18 and in patients with heart failure, 19 but nothing was known about the effects of training in DEX-treated SHR. Therefore, the objective of the present study was to investigate the effects of DEX treatment and aerobic training on arterial pressure and cardiac remodeling process in SHR.…”