Calcium dobesilate potentiates endothelium‐derived hyperpolarizing factor‐mediated relaxation of human penile resistance arteries

We have evaluated the participation of endothelium‐derived hyperpolarizing factor (EDHF) in the endothelium‐dependent relaxation of isolated human penile resistance arteries (HPRA) and human corpus cavernosum (HCC) strips. In addition, the effect of the angioprotective agent, calcium dobesilate (DOBE), on the endothelium‐dependent relaxation of these tissues was investigated. Combined inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) nearly abolished the endothelium‐dependent relaxation to acetylcholine (ACh) in HCC, while 60% relaxation of HPRA was observed under these conditions. Endothelium‐dependent relaxation of HPRA resistant to NOS and COX inhibition was prevented by raising the extracellular concentration of K + (35 m M ) or by blocking Ca 2 + ‐activated K + channels, with apamin (APA; 100 n M ) and charybdotoxin (CTX; 100 n M ), suggesting the involvement of EDHF in these responses. Endothelium‐dependent relaxation to ACh was markedly enhanced by DOBE (10 μ M ) in HPRA but not in HCC. The potentiating effects of DOBE on ACh‐induced responses in HPRA, remained after NOS and COX inhibition, were reduced by inhibition of cytochrome P 450 oxygenase with miconazole (0.3 m M ) and were abolished by high K + or a combination of APA and CTX.In vivo , DOBE (10 mg kg −1 i.v.) significantly potentiated the erectile responses to cavernosal nerve stimulation in male rats. EDHF plays an important role in the endothelium‐dependent relaxation of HPRA but not in HCC. DOBE significantly improves endothelium‐dependent relaxation of HPRA mediated by EDHF and potentiates erectile responses in vivo . Thus, EDHF becomes a new therapeutic target for the treatment of erectile dysfunction (ED) and DOBE could be considered a candidate for oral therapy for ED.British Journal of Pharmacology (2003) 139 , 854–862. doi: 10.1038/sj.bjp.0705293