Plasma immunoreactive endothelin-1 in experimental malignant hypertension.
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.
Kohno
M
M
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Murakawa
K
K
Horio
T
T
Yokokawa
K
K
Yasunari
K
K
Fukui
T
T
Takeda
T
T
D000375:Aging / Q000378:metabolism; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002110:Caffeine; D003404:Creatinine / Q000097:blood; D003900:Desoxycorticosterone; D016232:Endothelins / Q000097:blood*; D006801:Humans; D006974:Hypertension, Malignant / Q000097:blood* / Q000139:chemically induced; D006978:Hypertension, Renovascular / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012078:Renal Artery Obstruction / Q000378:metabolism; D012083:Renin / Q000097:blood; D013599:Systole
D016232:Endothelins; D000804:Angiotensin II; D010656:Phenylephrine; D002110:Caffeine; D003900:Desoxycorticosterone; D003404:Creatinine; D012083:Renin