Upregulation of endothelin-1 binding in tissues of salt-loaded stroke-prone spontaneously hypertensive rats
Upregulation of endothelin-1 binding in tissues of salt-loaded stroke-prone spontaneously hypertensive rats
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DOI：
10.1139/y02-032
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发表时间：
2002-05-01
影响因子：
2.1
通讯作者：
Jeng, AY
中科院分区：
文献类型：
--
作者：
Savage, P;Jeng, AY
在7周龄开始维持1%NaCl饮用溶液后，易卒中的自发性高血压大鼠（SHRsp）发展为严重的高血压和卒中;大多数在16周前死亡。这些疾病演变的机制仍不清楚。内皮素-1（ET-1）是一种有效的肽类血管收缩剂，与多种心血管、肾脏和中枢神经系统疾病的发病机制有关。本研究的目的是比较[I-125]ET-1与16周龄SHRsp和年龄匹配的血压正常的Wistar-Kyoto大鼠（WKY）的脑、心、肾、肝和脾膜制剂的结合。除脑外（SHRsp：17 +/- 1 pM; WKY：24 +/-1 pM），[I-125]ET-1与两种品系相应组织结合的K-D值无显著差异。相比之下，在SHRsp的脑、心脏、肾脏和肝脏中测得的B-max值是WKY对应物的1.5至2.1倍。特异性ETA受体拮抗剂BQ-123或特异性ETB受体激动剂sarafotoxin S6 c竞争[I-125]ET-1与膜制剂的结合，揭示了两种大鼠品系相应组织中ETA和ETB受体亚型的相似比例。这些结果表明，ET-1结合上调SHRsp，并建议ET-1可能发挥的病理生理作用，在这种动物模型的遗传性高血压。
Upon maintained on a 1% NaCl drinking solution beginning at 7 weeks of age, the stroke-prone spontaneously hypertensive rat (SHRsp) developed severe hypertension and stroke; most died by 16 weeks. The mechanism by which these diseases evolve remains unclear. Endothelin-1 (ET-1) is a potent, peptidic vasoconstrictor and is implicated in the pathogenesis of various cardiovascular, renal, and central nervous system diseases. The purpose of the present study was to compare the binding of [I-125]ET-1 to the brain, heart, kidney, liver, and spleen membrane preparations of 16-week-old SHRsp and age-matched normotensive Wistar-Kyoto rats (WKY). The K-D values for [I-125]ET-1 binding to the corresponding tissues of the two strains were not significantly different, except in the brain (SHRsp: 17 +/- 1 pM; WKY: 24 +/- 1 pM). In contrast, the B-max values measured in the brain, heart, kidney, and liver of SHRsp were 1.5- to 2.1-fold greater than those of their WKY counterparts. Competition of [I-125]ET-1 binding to the membrane preparations by the specific ETA receptor antagonist BQ-123 or the specific ETB receptor agonist sarafotoxin S6c revealed a similar proportion of ETA and ETB receptor subtypes in the corresponding tissues of the two rat strains. These results indicate that ET-1 binding is upregulated in SHRsp and suggest that ET-1 may play a pathophysiological role in this animal model of genetic hypertension.