Down‐regulation of endothelin‐B receptor sites in cavernosal tissue of hypercholesterolaemic rabbits

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Abstract
Objective: To investigate the density and distribution of endothelin‐1 (ET‐1) and endothelin receptor subtypes in cavernosal tissue of healthy New Zealand White (NZW) rabbits (controls) and to assess any changes in a genetic model of hypercholesterolaemia (the Watanabe rabbit).Materials and methods: Penises were excised from six hypercholesterolaemic (HC) rabbits 6 months after birth. Low‐and high‐resolution autoradiography was performed on cavernosal sections using radioligands for ET‐1, endothelin A (ETA ) and endothelin B (ETB ) receptors, and the autoradiographs analysed densitometrically. The results were compared with those from six age‐matched control rabbits. Immunohistochemical localization of ET‐1‐like immunoreactivity was also performed on adjacent cavernosal sections.Results: ET‐1, ETA and ETB receptor binding sites were primarily localized to the smooth muscle cells of the corpus cavernosum and the endothelium lining the cavernosal spaces. There was a significant decrease in ETB receptor binding sites in cavernosal tissue from HC rabbits when compared to age‐matched healthy controls.Conclusions: The findings suggest that ET‐1 may have a role in the pathophysiology of erectile dysfunction in HC. These effects may partly be due to enhanced vasoconstrictor actions and smooth muscle cell proliferation, consequent on a reduction in endothelial ETB receptors.