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Down-regulation of endothelin-B receptor sites in cavernosal tissue of hypercholesterolaemic rabbits
M E Sullivan1, M R Dashwood, C S Thompson
1Department of Urology, Royal Free Hampstead NHS Trust and School of Medicine, London, UK.
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.