Augmented expression of tissue endothelin-1 messenger RNA is a common feature in hypertensive rats

Recent studies revealed important roles for endothelin-1 (ET-1) in the path ogenesis of hypertension. Whether ET-1 could be a primary cause of hyperten sion or a secondary factor associated with hypertension, however remains un known. In this study, we determined plasma ET-1 levels and the expression o f ET-1 mRNA in tissues of rats rendered hypertensive using distinct mechani sms: deoxycorticosterone acetate (DOCA)-salt hypertension; N-G-nitro-L-argi nine-methyl ester- (L-NAME) induced hypertension; and spontaneously hyperte nsive rats (SHR-SP). ET-1 mRNA expression level was determined by reverse t ranscriptase polymerase chain reaction (RT-PCR) followed by Southern blotti ng. There was no significant difference in plasma ET-1 levels between the h ypertensive rats and normotensive rats. By contrast, ET-1 mRNA level was si gnificantly increased in various tissues including the adrenal, lung, kidne y and brain of these hypertensive rats compared with control rats. Thus, ET -1 gene expression was ubiquitously augmented in tissues of hypertensive ra ts irrespective of the cause of the hypertension. The results suggest that the increase in ET-1 expression is not the primary cause of hypertension bu t a secondary outcome which may further exacerbate the hypertension.