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β-肾上腺素能受体对自发性高血压大鼠肾脏白细胞介素-6和肿瘤坏死因子的作用

Role of beta-adrenoceptor on renal interleukin-6 and tumor necrosis factor in spontaneously hypertensive rats.

作者信息

Nakamura A, Johns E J, Abe T, Kohsaka T

机构信息

Department of Paediatrics, Teikyo University School of Medicine, Tokyo, Japan.

出版信息

Life Sci. 1998;62(26):2407-16. doi: 10.1016/s0024-3205(98)00224-0.

DOI:10.1016/s0024-3205(98)00224-0
PMID:9651107
Abstract

We have shown previously in the spontaneously hypertensive rat (SHR) kidney that interleukin-6 (IL-6) and tumor necrosis factor (TNF) mRNA levels were low under conditions of acute anaesthesia and surgical stress. The reasons for the suppression of IL-6 and TNF gene expression in the SHR were investigated by examining the influence of enhanced beta-adrenergic stimulation, high blood pressure, and renal function (renal blood flow, glomerular filtration rate, plasma creatinine levels) on renal IL-6 and TNF mRNAs. The experiments were performed by means of the following three studies; (1) SHR and Wistar rats at 4, 7, 9 week old were injected with lipopolysaccaride (LPS), and then a relationship between blood pressure levels and IL-6 and TNF mRNA levels were estimated, (2) isoproterenol and propranolol were administered into SHR and WKY rats, and the levels of IL-6 and TNF mRNA were compared, (3) under condition of anaesthesia and surgical stress, blood pressure and renal functions in SHR were measured, and then the relationships between these factors and IL-6 or TNF mRNA levels were analyzed. Renal IL-6 and TNF mRNAs in SHR remained low even though blood pressure increased with age and there was no significant correlation between IL-6 or TNF mRNA levels and values of blood pressure or renal function under anaesthesia and surgical stress. However, the inhibition of the IL-6 and TNF mRNAs in SHR was prevented by propranolol treatment. These results suggested that suppression of IL-6 and TNF mRNAs in the SHR kidney could be due to overactivity of beta-adrenergic influences which may importantly contribute to the development of hypertension.

摘要

我们之前在自发性高血压大鼠(SHR)的肾脏中发现,在急性麻醉和手术应激条件下,白细胞介素-6(IL-6)和肿瘤坏死因子(TNF)的mRNA水平较低。通过研究增强的β-肾上腺素能刺激、高血压和肾功能(肾血流量、肾小球滤过率、血浆肌酐水平)对肾脏IL-6和TNF mRNA的影响,来探究SHR中IL-6和TNF基因表达受抑制的原因。实验通过以下三项研究进行:(1)给4周龄、7周龄和9周龄的SHR和Wistar大鼠注射脂多糖(LPS),然后评估血压水平与IL-6和TNF mRNA水平之间的关系;(2)给SHR和WKY大鼠注射异丙肾上腺素和普萘洛尔,比较IL-6和TNF mRNA的水平;(3)在麻醉和手术应激条件下,测量SHR的血压和肾功能,然后分析这些因素与IL-6或TNF mRNA水平之间的关系。尽管SHR的血压随年龄增长而升高,但肾脏IL-6和TNF mRNA仍保持较低水平,并且在麻醉和手术应激下,IL-6或TNF mRNA水平与血压值或肾功能之间无显著相关性。然而,普萘洛尔治疗可防止SHR中IL-6和TNF mRNA的抑制。这些结果表明,SHR肾脏中IL-6和TNF mRNA的抑制可能是由于β-肾上腺素能影响过度活跃,这可能对高血压的发展起重要作用。

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