Increased renal medullary endothelin-1 synthesis in prehypertensive DOCA- and salt-treated rats

To investigate the role of renal endothelin-1 (ET-1) synthesis in water-sodium homeostasis, we measured mRNA expressions, protein levels, enzyme activity, and receptor binding of the renal ET-1 system in a DOCA- and salt-treated rat model. Male Wistar rats were divided into control and DOCA- and salt-treated (DOCA-Salt) groups. The DOCA-Salt group received 25 mg/kg body wt DOCA and was maintained on 1% NaCl drinking water. Rats were killed on days 1, 2, 4, and 10 of the experiment. Urinary ET-1-like immunoreactivity significantly increased from the second day in the DOCA-Salt group and correlated well with the urinary sodium excretion rate (r = 0.81, P < 0.001). Renal endothelin-converting enzyme (ECE) activity, ET-1, and ECE-1 mRNA expressions were significantly increased in the renal medullary area of DOCA-Salt rats. In situ hybridization and immunohistochemical studies showed that the increase in ET-1 synthesis was mainly localized in the inner medullary collecting ducts. The maximum binding of endothelin B receptor also increased from the second day in the renal medulla of the DOCA-Salt group. Our results suggest that renal medullary synthesized ET-1 may be a natriuretic factor and may participate in the intrarenal regulation of water and salt homeostasis in prehypertensive DOCA-and salt-treated rats.