ALTERATIONS IN ENDOTHELIN B-RECEPTOR-SITES IN CAVERNOSAL TISSUE OF DIABETIC RABBITS - POTENTIAL RELEVANCE TO THE PATHOGENESIS OF ERECTILE DYSFUNCTION

Purpose: Diabetes Mellitus (DM) is a major risk factor for erectile dy sfunction in both patients and animal models, The pathogenesis of this dysfunction has not been fully elucidated. However, alterations in th e synthesis of a number of vasoactive compounds, such as nitric oxide (NO) and prostacyclin (PGI(2)), have been reported in various diabetic tissues. The interaction between NO, PGI(2) and endothelin-1 (ET-1), a powerful vasoconstrictor and smooth muscle cell mitogen, is thought to be important in maintaining vascular tone and the erectile process. We investigated the density and distribution of ET-1 and endothelin r eceptor subtypes in cavernosal tissue and assessed any changes brought about by DM in a rabbit model. Materials and Methods: DM was induced in New Zealand White rabbits using alloxan. Penises were excised from the diabetic rabbits three months (n = 6) and six months in = 6) after the induction of DM. Low and high resolution autoradiography was perf ormed using radioligands for ET-1, endothelin A (ETA) and endothelin B (ETB) receptors and were analyzed densitometrically. The results were compared with those from six age-matched healthy control rabbits for each group. Immunohistochemical localization of ET-1 immunoreactivity was also performed, together with ultrastructural evaluation of the co rpus cavernosum. 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. A significant in crease in ETB receptor binding sites was found only in cavernosal tiss ue six months after induction of DM, when compared with age-matched he althy controls. These receptor changes were accompanied by ultrastruct ural changes in the corpus cavernosum indicative of an early, atherosc lerosis-like process. Conclusions: The autoradiographic and immunohist ochemical findings in this study suggest that ET-1 may have a role in the pathophysiology of diabetic ED. This peptide may be released in an autocrine fashion causing cavernosal smooth muscle cell (CSMC) contra ction and/or proliferation.