1. ¹Wolfson Institute for Biomedical Research, University College London, Gower Street, Cruciform Building, London, UK
2. ²The St Peter's Andrology Centre, University College London, London, UK

Correspondence: S Cellek, MD, PhD, Wolfson Institute for Biomedical Research, University College London, Gower Street, Cruciform Building, London WC1E 6BT, UK. E-mail: s.cellek@ucl.ac.uk

Received 3 September 2003; Revised 9 January 2004; Accepted 17 February 2004; Published online 18 March 2004.

Abstract

We compared the effects of a nitric oxide (NO)-releasing sildenafil (NCX-911), NO-independent soluble guanylate cyclase activator (BAY41-2272) and sildenafil on the anococcygeus muscle from streptozotocin-induced 16-weeks diabetic rats. NCX-911, BAY41-2272 and sildenafil reduced the phenylephrine-induced tone in the control group (EC₅₀=1088.8165.0, 151.69.3 and 827.1167.3 nM, respectively). The potencies of NCX-911 and BAY41-2272 were not altered, but that of sildenafil was significantly reduced in the diabetic group. EC₅₀ values for NCX-911, BAY41-2272 and sildenafil in the diabetic group were 1765.9303.5, 209.727.3 and 2842.2640.3 nM, respectively (P<0.05 for sildenafil). Nitrergic relaxation responses were significantly decreased in the diabetic group. The remaining nitrergic relaxation responses were potentiated by BAY41-2272 but not by sildenafil or NCX-911. These results confirm that endogenous NO derived from nitrergic nerves is significantly decreased in diabetes, and suggest that NO-releasing PDE5 inhibitors and NO-independent soluble guanylate cyclase activators could be more useful than PDE5 inhibitors in the treatment of ED in long-term diabetes.