DOWN-REGULATION OF ENDOTHELIN-B RECEPTOR-SITES IN CAVERNOSAL TISSUE OF HYPERCHOLESTEROLEMIC RABBITS

Objective To investigate the density and distribution of endothelin-1 (ET-1) and endothelin receptor subtypes in cavernosal tissue of health y New Zealand White (NZW) rabbits (controls) and to assess any changes in a genetic model of hypercholesterolaemia (the Watanabe rabbit). Ma terials and methods Penises were excised from sis hypercholesterolaemi c (HC) rabbits 6 months after birth, Low-and high-resolution autoradio graphy was performed on cavernosal sections using radioligands for ET- 1, endothelin A (ETA) and endothelin B (ETB) receptors, and the autora diographs analysed densitometrically. The results were compared with t hose from six age-matched control rabbits, Immunohistochemical localiz ation of ET-1-like immunoreactivity was also performed on adjacent cav ernosal sections. Results ET-1, ETA and ETB receptor binding sites wer e primarily localized to the smooth muscle cells of the corpus caverno sum and the endothelium lining the cavernosal spaces, There was a sign ificant decrease in ETB receptor binding sites in cavernosal tissue fr om HC rabbits when compared to age-matched healthy controls. Conclusio ns The findings suggest that ET-1 may have a role in the pathophysiolo gy of erectile dysfunction in HC, These effects map partly be due to e nhanced vasoconstrictor actions and smooth muscle cell proliferation, consequent on a reduction in endothelial ETB receptors.