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

Abstract

Introduction: Dexamethasone (DEX)-induced hypertension and cardiac remodeling are still unclear, especially in spontaneously hypertensive rats (SHR). On the other side, exercise training is a good strategy to control hypertension. Therefore, this study investigated the effects of DEX treatment and physical training on arterial pressure and cardiac remodeling in SHR. Material and Methods: SHR underwent treadmill training (5 days/week, 1h/session, at 50-60% of maximal capacity, 0% degree, 75 days) and received low-dose of DEX (50µg/kg, s.c.) during the last 15 days. Sedentary Wistar rats (W) were used as control. Echocardiography and artery catheterization were performed for cardiac remodeling and function, arterial pressure and autonomic nervous system analyses. In addition, left ventricle (LV) capillary density, myocyte diameter and collagen deposition area were analyzed using specific histological staining. Results: Low-dose of DEX treatment did not exacerbate arterial pressure of SHR and trained groups had lower values, regardless of DEX. DEX and training decreased relative left ventricle wall thickness (RWT) and determined LV angiogenesis (+19%) and lower collagen deposition area (−22%). In addition, it determined increased left ventricular diastolic diameter. These changes were followed by improvements on systolic and diastolic function, since it was observed increased posterior wall shortening velocity (PWSV) and reduced isovolumetric relaxation time (IVRT). Conclusion: In conclusion, this study is unique to indicate that low-dose of DEX treatment does not exacerbate arterial pressure in SHR and, when associated with training, it improves LV systolic and diastolic function, which may be due to LV angiogenesis and reduction of wall collagen deposition area.

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

“…The results of the present study showed that low‐dose (50 μg/kg) of DEX treatment changed the autonomic control to the heart in Wistar rats, which in part contributed to increase BP, but the higher sympathetic drive to the heart, already present in SHR, was maintained after the DEX treatment period. These results agree with our recent publication (Duchatsch et al, 2020), which was the first study investigating the effects of this dose of DEX and exercise training in SHR.…”

“…The first part of this present study showed that SHR presented higher BP accompanied by autonomic unbalance to the heart, represented by higher LF and lower HF compared with Wistar rats, therefore confirming that hypertension, already installed in SHR, is generally accompanied by inappropriate neural adjustments (Bertagnolli et al, 2006; Duchatsch et al, 2020; Masson et al, 2015; Stern et al, 2015).…”

“…Because the progress of hypertension is normally followed by cardiac remodeling (Cohn et al, 2000; Duchatsch et al, 2020; Han et al, 2015; Hernandez et al, 2013; Pagan et al, 2015; Pagan et al, 2019; Rossoni et al, 2011), this present study evaluated the structural and functional changes determined by hypertension through the echocardiographic analysis and confirmed some previous results recently found by our group and others (Duchatsch et al, 2020; Han et al, 2015; J. Li et al, 2019) that SHR, even at 5 months, had higher LV relative wall thickness and increased LVMI, which can be induced by pressure overload (Bernardo et al, 2010). In fact, this increased LV RWT probably contributed to the reduced internal diameter during systolic and diastolic periods, as observed in these rats.…”

“…In agreement, besides DEX induced hypertension in Wistar rats in this present study, it did not significantly alter the cardiac structural or functional parameters, assessed by echocardiographic and histological techniques. Data about the effects of DEX on myocardial remodeling are still controversial, mainly because some authors showed that DEX causes cardiomyocyte hypertrophy and cardiac dysfunction (De et al, 2011; de Salvi Guimaraes et al, 2017; Dodic et al, 2001; F. N. Macedo et al, 2020; Muangmingsuk et al, 2000; Ren et al, 2012) and other authors show a cardioprotective effect of DEX (Aguilar et al, 2014; Chen et al, 2005; Duchatsch et al, 2020; Rao et al, 2001; Ren et al, 2012; Xia et al, 2007; Xu et al, 2011).…”

“…Because hypertensive individuals may be clinically treated with DEX, for numerous purposes, it is important to evaluate the effects of DEX treatment on hypertensive animals. Recently, our group showed that low‐dose of DEX treatment does not exacerbate blood pressure in hypertensive animals (Duchatsch et al, 2020), as it does in normotensive ones, but the effects of DEX treatment on arterial stiffness of hypertensive rats have not been investigated. Therefore, the aim of this present study was to evaluate the effects of DEX on hemodynamics, cardiac hypertrophy, and arterial stiffness in normotensive and hypertensive rats.…”