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

Abstract

Dexamethasone (DEX)‐induced hypertension is observed in normotensive rats, but little is known about the effects of DEX on spontaneously hypertensive animals (SHR). This study aimed to evaluate the effects of DEX on hemodynamics, cardiac hypertrophy and arterial stiffness in normotensive and hypertensive rats. Wistar rats and SHR were treated with DEX (50 μg/kg s.c., 14 d) or saline. Pulse wave velocity (PWV), echocardiographic parameters, blood pressure (BP), autonomic modulation and histological analyses of heart and thoracic aorta were performed. SHR had higher BP compared with Wistar, associated with autonomic unbalance to the heart. Echocardiographic changes in SHR (vs. Wistar) were suggestive of cardiac remodeling: higher relative wall thickness (RWT, +28%) and left ventricle mass index (LVMI, +26%) and lower left ventricle systolic diameter (LVSD, −19%) and LV diastolic diameter (LVDD, −10%), with slightly systolic dysfunction and preserved diastolic dysfunction. Also, SHR had lower myocardial capillary density and similar collagen deposition area. PWV was higher in SHR due to higher aortic collagen deposition. DEX‐treated Wistar rats presented higher BP (~23%) and autonomic unbalance. DEX did not change cardiac structure in Wistar, but PWV (+21%) and aortic collagen deposition area (+21%) were higher compared with control. On the other side, DEX did not change BP or autonomic balance to the heart in SHR, but reduced RWT and LV collagen deposition area (−12% vs. SHRCT). In conclusion, the results suggest a differential effect of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats.

Benefits of combined exercise training on arterial stiffness and blood pressure in spontaneously hypertensive rats treated or not with dexamethasone

“…Treatment with dexamethasone (Decadron ® , 50 μg/kg of body weight, s. c. Aché Laboratories, Guarulhos, SP, Brazil) was daily performed in SHR rats at 9 a.m. for 14 days (once per day) and control SHR received saline at the same volume as DEX. This DEX dosage was elected based on our previous results, because it showed less undesirable side effects in Wistar rats and did not increase BP in SHR (Tardelli et al, 2021). Body weight was weekly measured during training period (8 weeks) and daily measured during DEX treatment period, as shown in Figure 1, which illustrates the experimental design.…”

“…Frontiers in Physiology frontiersin.org the fibers of collagen in red. The quantification of the myocardial collagen area and the percentage (%) of the collagen area were automatically calculated by the ImageJ software, based on the detection of red staining in a given area, as published (Miotto et al, 2021b;Duchatsch et al, 2021;Tardelli et al, 2021). Myocardial sections of 5 μm thick were stained with hematoxylin and eosin staining (H&E, Easy Path, SP) for analysis of myocyte diameter (longitudinal section) and capillary density (transversal section), as published (Herrera et al, 2016;Miotto et al, 2021b;Duchatsch et al, 2021;Tardelli et al, 2021).…”

“…The quantification of the myocardial collagen area and the percentage (%) of the collagen area were automatically calculated by the ImageJ software, based on the detection of red staining in a given area, as published (Miotto et al, 2021b;Duchatsch et al, 2021;Tardelli et al, 2021). Myocardial sections of 5 μm thick were stained with hematoxylin and eosin staining (H&E, Easy Path, SP) for analysis of myocyte diameter (longitudinal section) and capillary density (transversal section), as published (Herrera et al, 2016;Miotto et al, 2021b;Duchatsch et al, 2021;Tardelli et al, 2021). The steps of HE staining were performed as follows: xylene (5 min), xylene (5 min), 100% alcohol (3 min), 90% alcohol (3 min), 80% alcohol (3 min), 70% alcohol (3 min) and washed in running distilled water (10 min).…”

“…All sections were documented at 200X magnification. The quantification of the collagen area and the percentage (%) of the area of collagen were automatically calculated by the ImageJ software, based on Frontiers in Physiology frontiersin.org the detection of red staining in a given area, as published (Tardelli et al, 2021). Sections of 10 μm thick were performed by disposable blades, placed on glass slides and later be stained with H&E for morphometric analyses.…”

“…From these values, the wall thickness was calculated [(OD-ID)/ 2], μm) and the wall/lumen ratio (W/L), as previously published (Fabricio et al, 2020;Miotto et al, 2021b;Tardelli et al, 2021).…”