Recent studies revealed important roles for endothelin-1 (ET-1) in the pathogenesis of hypertension. Whether ET-1 could be a primary cause of hypertension or a secondary factor associated with hypertension, however, remains unknown. In this study, we determined plasma ET-1 levels and the expression of ET-1 mRNA in tissues of rats rendered hypertensive using distinct mechanisms: deoxycorticosterone acetate (DOCA)-salt hypertension; NG-nitro-L-arginine-methyl ester-(L-NAME) induced hypertension; and spontaneously hypertensive rats (SHR-SP). ET-1 mRNA expression level was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blotting. There was no significant difference in plasma ET-1 levels between the hypertensive rats and normotensive rats. By contrast, ET-1 mRNA level was significantly increased in various tissues including the adrenal, lung, kidney and brain of these hypertensive rats compared with control rats. Thus, ET-1 gene expression was ubiquitously augmented in tissues of hypertensive rats irrespective of the cause of the hypertension. The results suggest that the increase in ET-1 expression is not the primary cause of hypertension but a secondary outcome which may further exacerbate the hypertension.
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Tokyo, Japan
Address correspondence and reprint requests to Mitsuhide Naruse, Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. E-mail: RXK00754@niftyserve.or.jp
© 2000 Lippincott Williams & Wilkins, Inc.