Expression of ETA and ETB receptor in adventitial fibroblasts

Abstract

Objective: The adventitia has been recognized to play important roles in vascular remodeling and contraction. We recently demonstrated that adventitial fibroblasts are able to express endothelin‐1 (ET‐1) in response to angiotensin II (ANG II). However, it is unclear whether the ET‐1 receptors are expressed in the adventitia. We therefore examined the expression of both the ETA/B receptors and the roles of these two types of receptors in collagen synthesis and ET‐1 clearance in adventitial fibroblasts.Methods and Results: Adventitial fibroblasts were isolated and cultured from the thoracic mouse aorta. Cells were treated with ANG II (100 nM), the ET‐1 receptor antagonists (100 uM), BQ123 (ETA receptor) and/or BQ788 (ETB receptor). ET‐1 peptide levels were determined by ELISA, while ETA/B and collagen levels were determined by Western blot. ANG II increased ETA receptor protein as well as collagen in a similar fashion, reaching significance after 4, 6, and 24 hours treatment. ANG II induced collagen was reduced while in the presence of the ETA receptor antagonist suggesting the role of the ETA receptor in the regulation of the extracellular matrix. ANG II treatment also increased ETB receptor protein levels in time dependent manner. ANG II treatment in the presence of the ETB receptor antagonist significantly increased ET‐1 peptide levels, implicating the role of the ETB receptor in the clearance of the ET‐1 peptide.Conclusion: Both the ETA and ETB receptors are expressed in adventitial fibroblasts. The ETA receptor subtype mediates collagen I expression, while the ETB receptor may play a protective role through increasing the clearance of the ET‐1 peptide.