Endothelin‐1 and the Metalloproteases ECE and NEP in DOCA‐Salt Hypertensive Rats

Abstract

Endothelin‐1 (ET‐1) is thought to be a key player in DOCA‐salt induced hypertension. We hypothesized that the bioavailability of ET‐1 is controlled by tissue specific expression of the metalloproteases endothelin converting enzyme (ECE) and neutral endopeptidase (NEP). To test this hypothesis we measured ECE and NEP protein content in kidneys and hearts of DOCA‐salt treated rats 3 and 6 weeks after implantation of a 100 mg DOCA pellet combined with high salt drinking water. In addition, ET‐1 content was determined in these organs by RIA. During DOCA‐salt treatment, blood pressure was significantly elevated in association with increased kidney and heart weight. Despite the occurrence of structural damage in these organs (verified by histology), ECE, NEP, and ET‐1 content were not significantly altered 3 and 6 weeks after DOCA treatment (n=6/organ/group). These data indicate that both ET‐1 and metalloprotease content in the heart and kidneys do not contribute to the maintenance of hypertension in the DOCA‐salt rat model.This research was performed within the framework of project T2‐108 of the Dutch Top Institute Pharma.