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卡维地洛或氨氯地平对L-NAME高血压大鼠靶器官损害的影响:它们与血压变异性的关系。

Effects of carvedilol or amlodipine on target organ damage in L-NAME hypertensive rats: their relationship with blood pressure variability.

作者信息

Del Mauro Julieta S, Prince Paula D, Donato Martín, Fernandez Machulsky Nahuel, Morettón Marcela A, González Germán E, Bertera Facundo M, Carranza Andrea, Gorzalczany Susana B, Chiappetta Diego A, Berg Gabriela, Morales Celina, Gelpi Ricardo J, Taira Carlos A, Höcht Christian

机构信息

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Buenos Aires, Argentina.

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Físicoquímica, Instituto de Bioquímica y Medicina Molecular-Consejo Nacional de Investigaciones Científicas y Técnicas (IBIMOL-CONICET), Buenos Aires, Argentina.

出版信息

J Am Soc Hypertens. 2017 Apr;11(4):227-240. doi: 10.1016/j.jash.2017.02.007. Epub 2017 Mar 2.

Abstract

The aim of the study was to compare the effects of chronic oral treatment with carvedilol or amlodipine on blood pressure, blood pressure variability and target organ damage in N-nitro-l-arginine methyl ester (L-NAME) hypertensive rats. Wistar rats were treated with L-NAME administered in the drinking water for 8 weeks together with oral administration of carvedilol 30 mg/kg (n = 6), amlodipine 10 mg/kg (n = 6), or vehicle (n = 6). At the end of the treatment, echocardiographic evaluation, blood pressure, and short-term variability measurements were performed. Left ventricular and thoracic aortas were removed to assess activity of metalloproteinase 2 and 9 and expression levels of transforming growth factor β, tumor necrosis factor α, and interleukin 6. Histological samples were prepared from both tissues. Carvedilol and amlodipine induced a comparable reduction of systolic and mean arterial pressure and its short-term variability in L-NAME rats. The expression of transforming growth factor β, tumor necrosis factor α, and interleukin 6 decreased in both organs after carvedilol or amlodipine treatment and the activity of metalloproteinase was reduced in aortic tissue. Treatment with carvedilol or amlodipine completely prevented left ventricular collagen deposition and morphometric alterations in aorta. Oral chronic treatment with carvedilol or amlodipine significantly attenuates blood pressure variability and reduces target organ damage and biomarkers of tissue fibrosis and inflammation in L-NAME hypertensive rats.

摘要

本研究的目的是比较长期口服卡维地洛或氨氯地平对N-硝基-L-精氨酸甲酯(L-NAME)高血压大鼠血压、血压变异性和靶器官损伤的影响。将Wistar大鼠用饮用水中给予的L-NAME处理8周,同时口服30mg/kg卡维地洛(n = 6)、10mg/kg氨氯地平(n = 6)或赋形剂(n = 6)。在治疗结束时,进行超声心动图评估、血压和短期变异性测量。取出左心室和胸主动脉以评估金属蛋白酶2和9的活性以及转化生长因子β、肿瘤坏死因子α和白细胞介素6的表达水平。从两种组织制备组织学样本。卡维地洛和氨氯地平在L-NAME大鼠中引起收缩压和平均动脉压及其短期变异性的类似降低。卡维地洛或氨氯地平治疗后,两个器官中转化生长因子β、肿瘤坏死因子α和白细胞介素6的表达均降低,主动脉组织中金属蛋白酶的活性降低。卡维地洛或氨氯地平治疗完全预防了左心室胶原沉积和主动脉的形态学改变。长期口服卡维地洛或氨氯地平可显著减轻L-NAME高血压大鼠的血压变异性,并减少靶器官损伤以及组织纤维化和炎症的生物标志物。

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