Alterations in endothelin B receptor sites in cavernosal tissue of diabetic rabbits: potential relevance to the pathogenesis of erectile dysfunction

• Published in: The Journal of urology Vol. 158; no. 5; p. 1966
• Main Authors: Sullivan, M E, Dashwood, M R, Thompson, C S, Muddle, J R, Mikhailidis, D P, Morgan, R J
• Format: Journal Article
• Language: English
• Published: United States 01-11-1997
• Subjects: Animals; Autoradiography; Binding Sites - physiology; Blood Glucose - analysis; Body Weight; Cholesterol - blood; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - physiopathology; Endothelin-1 - analysis; Erectile Dysfunction - etiology; Immunohistochemistry; Male; Penis - chemistry; Penis - ultrastructure; Rabbits; Receptor, Endothelin B; Receptors, Endothelin - analysis; Receptors, Endothelin - physiology
• ISSN: 0022-5347
• DOI: 10.1016/S0022-5347(01)64195-8

Diabetes Mellitus (DM) is a major risk factor for erectile dysfunction in both patients and animal models. The pathogenesis of this dysfunction has not been fully elucidated. However, alterations in the synthesis of a number of vasoactive compounds, such as nitric oxide (NO) and prostacyclin (PGI2), have been reported in various diabetic tissues. The interaction between NO, PGI2 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 receptor subtypes in cavernosal tissue and assessed any changes brought about by DM in a rabbit model.
DM was induced in New Zealand White rabbits using alloxan. Penises were excised from the diabetic rabbits three months (n = 6) and six months (n = 6) after the induction of DM. Low and high resolution autoradiography was performed 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 corpus cavernosum.
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. A significant increase in ETB receptor binding sites was found only in cavernosal tissue six months after induction of DM, when compared with age-matched healthy controls. These receptor changes were accompanied by ultrastructural changes in the corpus cavernosum indicative of an early, atherosclerosis-like process.
The autoradiographic and immunohistochemical 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) contraction and/or proliferation.