Nakamura A, Kohsaka T, Johns E J
Department of Physiology, University of Birmingham, UK.
J Hypertens. 1994 Mar;12(3):239-43.
To determine whether renal interleukin-6 was produced constitutively under the normal physiological conditions and to evaluate the influence of hypertension development on interleukin-6 production in two different hypertensive models, the spontaneously hypertensive rat (SHR) and the two-kidney, one clip (2-K,1C) hypertensive rat.
In a chronic study, Wistar rats and SHR, aged 4, 5, 7 and 9 weeks, and 2-K,1C Goldblatt hypertensive rats, at 2 and 4 weeks after applying the clip, were anaesthetized, their blood pressures were measured and the kidneys were collected and renal interleukin-6 production estimated.
The rats were lightly anaesthetized with halothane and prepared for blood pressure measurement via a carotid artery cannula. Interleukin-6 production was estimated from the interleukin-6 messenger RNA (mRNA) present in the kidney tissue. The mRNA species (interleukin-6, beta-actin and renin) were measured by densitometric analysis of the autoradiographs following Northern blot hybridization.
The blood pressure was approximately 100 mmHg at all ages in the Wistar rats, but rose from 101 +/- 3 mmHg at age 4 weeks to 154 +/- 2 mmHg at age 9 weeks in the SHR (means +/- SEM, P < 0.01). Constitutive production of renal interleukin-6 could not be detected in either the Wistar rats or the SHR. In 2-K,1C rats the blood pressure was increased significantly at 2 and 4 weeks after clipping to 129 +/- 3 and 140 +/- 4 mmHg (means +/- SEM, both P < 0.01), respectively, and the renal renin mRNA concentration was increased significantly in the clipped and decreased in the non-clipped kidneys at 2 and 4 weeks after clipping. The renal interleukin-6 mRNA could not be measured in either clipped or non-clipped kidneys at either 2 or 4 weeks after clipping.
These findings demonstrate that renal interleukin-6 was not produced constitutively under normal physiological conditions. Moreover, in spite of the development of hypertension from two causes, genetic and renin-dependent, renal interleukin-6 was not expressed even though there is a deficit in immunological function in the SHR and damage to the renal tissue of the 2-K,1C rats.
确定在正常生理条件下肾脏是否组成性产生白细胞介素-6,并评估高血压发展对两种不同高血压模型(自发性高血压大鼠(SHR)和二肾一夹(2-K,1C)高血压大鼠)中白细胞介素-6产生的影响。
在一项慢性研究中,对4、5、7和9周龄的Wistar大鼠和SHR,以及夹闭后2周和4周的2-K,1C Goldblatt高血压大鼠进行麻醉,测量其血压,收集肾脏并评估肾脏白细胞介素-6的产生。
用氟烷轻度麻醉大鼠,通过颈动脉插管准备测量血压。根据肾脏组织中存在的白细胞介素-6信使核糖核酸(mRNA)评估白细胞介素-6的产生。在Northern印迹杂交后,通过对放射自显影片的光密度分析来测量mRNA种类(白细胞介素-6、β-肌动蛋白和肾素)。
Wistar大鼠在所有年龄段血压约为100 mmHg,但SHR的血压从4周龄时的101±3 mmHg升至9周龄时的154±2 mmHg(均值±标准误,P<0.01)。在Wistar大鼠或SHR中均未检测到肾脏白细胞介素-6的组成性产生。在2-K,1C大鼠中,夹闭后2周和4周血压分别显著升高至129±3和140±4 mmHg(均值±标准误,均P<0.01),夹闭后2周和4周,夹闭侧肾脏肾素mRNA浓度显著升高,未夹闭侧肾脏肾素mRNA浓度降低。夹闭后2周或4周,在夹闭侧或未夹闭侧肾脏中均未检测到肾脏白细胞介素-6 mRNA。
这些发现表明,在正常生理条件下肾脏不组成性产生白细胞介素-6。此外,尽管存在遗传和肾素依赖性两种原因导致的高血压发展,但即使SHR存在免疫功能缺陷且2-K,1C大鼠的肾组织受损,肾脏白细胞介素-6仍未表达。