Bolger G T, Liard F, Jodoin A, Jaramillo J
Department of Pharmacology, Bio Mega Inc., Laval, Que., Canada.
Can J Physiol Pharmacol. 1991 Mar;69(3):406-13. doi: 10.1139/y91-062.
The role of endothelin (ET-1) in mediating the development of blood pressure was investigated in the spontaneously hypertensive (SHR) rat using the Wistar-Kyoto (WKY) rat as the normotensive control. The following were characterized in both rat strains: age-dependent changes in mean arterial blood pressure (MAP), tissue (blood, lung, heart, and kidney) levels of immunoreactive ET-1 like related peptides (ET-1RP), aortic ring responses to ET-1, and specific high-affinity tissue (lung, atrium, ventricle, aorta, and kidney) binding sites for 125I-labelled ET-1. Commencing at age 10 weeks through to 12 weeks, SHR rats but not WKY rats developed a significant increase in MAP (from 152 +/- 7 to 189 +/- 3 mmHg) (1 mmHg = 133.32 Pa). However, in both WKY and SHR rats immunoreactive levels of ET-1RP increased (100 and 80%, respectively) throughout the same measurement period. The potency of ET-1 to contract aortic rings from SHR rats was slightly but not significantly greater than that for aortic rings from WKY rats, although aortic rings from SHR rats contracted in the presence of 0.5 nM ET-1, while those from WKY rats did not. The levels of immunoreactive ET-1RP were significantly reduced (32%) in the kidney and unchanged in the heart and lung of SHR rats compared with WKY rats. Specific 125I-labelled ET-1 binding sites displayed an increase and a significant decrease (24%) of density in the atrium and ventricle, respectively, a significant increase (31%) of affinity in the lung, and were unchanged in the kidney and aorta of SHR rats compared with WKY rats following the development of hypertension. The lack of a correlation between circulating levels of immunoreactive ET-1RP and the development of hypertension coupled with a lack of significant differences in vascular reactivity suggest that ET-1 is not the sole mediator of hypertension in this animal model. However, the tissue-specific changes in immunoreactive ET-1RP and 125I-labelled ET-1 binding sites suggest that ET-1 may be a partial mediator of hypertension and is subject to compensatory changes in response to the increased total peripheral resistance in SHR rats.
以内毒素（ET-1）在介导血压升高过程中的作用为研究对象，采用Wistar-Kyoto（WKY）大鼠作为正常血压对照，对自发性高血压（SHR）大鼠展开研究。对两种大鼠品系的以下指标进行了特征分析：平均动脉血压（MAP）的年龄依赖性变化、组织（血液、肺、心脏和肾脏）中免疫反应性ET-1样相关肽（ET-1RP）的水平、主动脉环对ET-1的反应以及125I标记的ET-1在特定高亲和力组织（肺、心房、心室、主动脉和肾脏）中的结合位点。从10周龄到12周龄，SHR大鼠的MAP显著升高（从152±7 mmHg升至189±3 mmHg）（1 mmHg = 133.32 Pa），而WKY大鼠未出现这种情况。然而，在相同的测量期间，WKY大鼠和SHR大鼠体内ET-1RP的免疫反应性水平均有所升高（分别升高了100%和80%）。ET-1使SHR大鼠主动脉环收缩的效力虽略高于WKY大鼠主动脉环，但差异不显著，不过在0.5 nM ET-1存在的情况下，SHR大鼠的主动脉环会收缩，而WKY大鼠的主动脉环则不会。与WKY大鼠相比，SHR大鼠肾脏中免疫反应性ET-1RP的水平显著降低（32%），心脏和肺中的水平则无变化。高血压形成后，与WKY大鼠相比，SHR大鼠心房和心室中特定的125I标记ET-1结合位点的密度分别增加和显著降低（24%），肺中的亲和力显著增加（31%），肾脏和主动脉中的结合位点则无变化。免疫反应性ET-1RP的循环水平与高血压的发生之间缺乏相关性，同时血管反应性也无显著差异，这表明在该动物模型中，ET-1并非高血压的唯一介导因素。然而，免疫反应性ET-1RP和125I标记的ET-1结合位点的组织特异性变化表明，ET-1可能是高血压的部分介导因素，并且会因SHR大鼠总外周阻力增加而发生代偿性变化。
