Kohno M, Murakawa K, Horio T, Yokokawa K, Yasunari K, Fukui T, Takeda T
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Hypertension. 1991 Jul;18(1):93-100. doi: 10.1161/01.hyp.18.1.93.
We measured plasma concentrations of immunoreactive endothelin-1 (irET-1) in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in malignant hypertension caused by deoxycorticosterone acetate (DOCA)-salt administration in SHR. We also measured concentrations of this peptide in another model of malignant hypertension, the two-kidney, one clip (2K1C) renovascular hypertensive rats chronically given caffeine. Plasma irET-1 concentrations in young (6-week-old) and mature (18-week-old) SHR did not differ from those of age-matched Wistar-Kyoto (WKY) rats. Four weeks of treatment with DOCA-salt increased blood pressure, blood urea nitrogen, serum creatinine, and plasma irET-1 in SHR but not in WKY rats. Eight weeks of DOCA-salt treatment further increased these values in SHR. Plasma irET-1 concentrations were not increased in the 2K1C rats. Six weeks of caffeine administration increased blood pressure, blood urea nitrogen, serum creatinine, plasma renin activity, and plasma irET-1 in the 2K1C rats but not in the sham-operated rats. High-performance liquid chromatographic profiles of plasma extracts pooled from these rats with malignant hypertension showed that a major component of irET-1 eluted in the position of synthetic ET-1 (1-21). Furthermore, acute hypertension induced by angiotensin II or phenylephrine did not affect the plasma irET-1 concentration in rats. The results suggested that the plasma ET-1 concentration is increased in rat models of malignant hypertension and that the high blood pressure itself is not the main factor involved in the increase of plasma ET-1.
我们测量了自发性高血压大鼠（SHR）高血压前期和高血压期以及通过给SHR注射醋酸脱氧皮质酮（DOCA）-盐诱导的恶性高血压中免疫反应性内皮素-1（irET-1）的血浆浓度。我们还测量了另一种恶性高血压模型——长期给予咖啡因的两肾一夹（2K1C）肾血管性高血压大鼠中该肽的浓度。年轻（6周龄）和成熟（18周龄）SHR的血浆irET-1浓度与年龄匹配的Wistar-Kyoto（WKY）大鼠的浓度无差异。DOCA-盐治疗4周使SHR的血压、血尿素氮、血清肌酐和血浆irET-1升高，但WKY大鼠未出现此情况。DOCA-盐治疗8周使SHR的这些值进一步升高。2K1C大鼠的血浆irET-1浓度未升高。给予咖啡因6周使2K1C大鼠的血压、血尿素氮、血清肌酐、血浆肾素活性和血浆irET-1升高，但假手术大鼠未出现此情况。从这些患有恶性高血压的大鼠中收集的血浆提取物的高效液相色谱图谱显示，irET-1的主要成分在合成ET-1（1-21）的位置洗脱。此外，血管紧张素II或去氧肾上腺素诱导的急性高血压不影响大鼠的血浆irET-1浓度。结果表明，在大鼠恶性高血压模型中血浆ET-1浓度升高，且高血压本身不是血浆ET-1升高的主要因素。
