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地塞米松对正常血压大鼠和自发性高血压大鼠动脉僵硬度、心肌重塑及血压的不同影响。

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

作者信息

Tardelli Lidieli P, Duchatsch Francine, Herrera Naiara A, Vicentini Carlos Alberto, Okoshi Katashi, Amaral Sandra L

机构信息

Joint Graduate Program in Physiological Sciences, PIPGCF UFSCar/UNESP, São Carlos, Brazil.

Department of Biology, School of Sciences, São Paulo State University (UNESP), Bauru, Brazil.

出版信息

J Appl Toxicol. 2021 Oct;41(10):1673-1686. doi: 10.1002/jat.4155. Epub 2021 Feb 24.

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. SHR ). In conclusion, the results suggest a differential effect of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats.

摘要

在正常血压大鼠中可观察到地塞米松(DEX)诱导的高血压,但关于DEX对自发性高血压动物(SHR)的影响知之甚少。本研究旨在评估DEX对正常血压和高血压大鼠的血流动力学、心脏肥大和动脉僵硬度的影响。将Wistar大鼠和SHR用DEX(50μg/kg皮下注射,14天)或生理盐水处理。进行了脉搏波速度(PWV)、超声心动图参数、血压(BP)、自主神经调节以及心脏和胸主动脉的组织学分析。与Wistar大鼠相比,SHR的血压更高,伴有心脏自主神经失衡。SHR(与Wistar大鼠相比)的超声心动图变化提示心脏重构:相对壁厚度(RWT,增加28%)和左心室质量指数(LVMI,增加26%)更高,而左心室收缩直径(LVSD,降低19%)和左心室舒张直径(LVDD,降低10%)更低,伴有轻度收缩功能障碍和舒张功能保留。此外,SHR的心肌毛细血管密度较低,胶原沉积面积相似。由于主动脉胶原沉积增加,SHR的PWV更高。DEX处理的Wistar大鼠血压更高(约23%)且存在自主神经失衡。DEX未改变Wistar大鼠的心脏结构,但与对照组相比,PWV(增加21%)和主动脉胶原沉积面积(增加21%)更高。另一方面,DEX未改变SHR的血压或心脏自主神经平衡,但降低了RWT和左心室胶原沉积面积(与SHR相比降低12%)。总之,结果表明地塞米松对正常血压和自发性高血压大鼠的动脉僵硬度、心肌重构和血压有不同的影响。

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