There is convincing evidence that the prevalence of erectile dysfunction is increased among men with ischaemic heart disease. This association may be attributed to the fact that both erectile dysfunction and ischaemic heart disease share similar risk factors (e.g. hypertension, dyslipidaemia, diabetes and smoking). Nitric oxide (NO) activity is adversely affected, in penile and vascular tissue, by these risk factors. It is therefore not surprising that a defect in NO activity is thought to play a role in the pathogenesis of both erectile dysfunction and ischaemic heart disease. We consider this evidence and propose that defective NO activity provides a unifying explanation for the association between these two conditions. Further research in this area may improve our understanding of the pathogenesis of cardiovascular diseases as a whole.

cancer tissue was determined by immunohistochemistry and Western blot analysis. RESULTS5HT caused a dose-dependent increase in the proliferation of HT1376 cells. The maximum increase in cell proliferation (12%; 12 samples, P < 0.001) was at 10 − 8 M as compared to the control at 72 h. At 10 − 4 M , 5HT 1A antagonist and 5HT 1B antagonist (SB224289 hydrochloride) had a 10% (12 samples, P < 0.001) and 93% (12, P < 0.001) inhibitory effect on HT1376 cell growth, respectively, compared to the control at 72 h. There was immunostaining for 5HT 1A and 5HT 1B receptors in HT1376 cells and malignant bladder tissue, confirming the presence of these two receptor subtypes. Western blot analysis showed the presence of 5HT 1A and 5HT 1B receptor proteins with bands of 46 kDa and 43 kDa, respectively. CONCLUSION5HT 1A and to a greater extent 5HT 1B antagonists significantly inhibit bladder cancer cell growth. This effect is probably mediated via the 5HT 1A and 5HT 1B receptors. These results highlight the potential use of 5HT 1A and 5HT 1B antagonists in the treatment of bladder cancer.

OBJECTIVE To assess whether the antineoplastic action of extracellular ATP seen in hormone‐refractory prostate cancer extends to other aggressive urological malignancies by investigating its effect in high‐grade bladder cancer cells in vitro and in vivo. MATERIALS AND METHODS HT‐1376 cells (human grade 3 transitional cell carcinoma) were incubated with various purinergic receptor agonists and antagonists and their effects on cell growth was examined in vitro. The presence of different P2 receptor mRNAs was determined using reverse transcriptase‐polymerase chain reaction. The effect of combining ATP with the cytotoxic agent mitomycin C (MMC) was also investigated. Models of tumour outgrowth in athymic mice were used to examine the effect of ATP on tumour growth in vivo. RESULTS HT‐1376 cells expressed P2X4,5,7 and P2Y1,2,4,6,11 receptor mRNA. ATP significantly reduced cell growth in a concentration‐dependent manner via the induction of P2 receptor‐mediated apoptosis. Pharmacological profiling implicated P2X5 and/or P2Y11 receptors in this antineoplastic response, the same receptor subtypes shown to be active in prostate adenocarcinoma, despite the differing cellular origin. ATP and MMC combined in an additive manner. Intraperitoneal injections of ATP significantly reduced the growth of implanted tumour cells by a combination of apoptosis and necrosis. CONCLUSIONS ATP effectively reduces the growth of high‐grade bladder cancer cells in vitro and in vivo. This highlights the potential use of ATP in the treatment of advanced urological malignancies irrespective of the cellular origin.

Objective To investigate the effect of superoxide dismutase (SOD, the enzyme that accelerates the breakdown of the superoxide anion, O 2 ± to H 2 O) on nitric oxide (NO)-mediated and electrical ®eld stimulated (EFS) relaxation in diabetic rabbit cavernosal smooth muscle. Materials and methods Diabetes was induced with alloxan (65 mg/kg) in six adult New Zealand White rabbits. After 6 months, cavernosal smooth muscle strips from age-matched controls and diabetic animals were mounted in organ baths. After precontraction with phenylephrine (10 mmol/L) in the presence of atropine (1 mmol/L), guanethidine (5 mmol/L) and indomethacin (10 mmol/L), relaxation responses to EFS (1±20 Hz), carbachol (10 x8 x10 x4 mol/L) and sodium nitroprusside (SNP, 10 x9 x10 x4 mol/L) were assessed in the presence and absence of SOD (100 IU/ mL). Results SNP-and carbachol-mediated (endotheliumindependent and -dependent, respectively) relaxations were impaired in the diabetic cavernosal smooth muscle strips compared with controls (concentration required for 50% inhibition, 1.4 mmol/L for diabetic and 0.75 mmol/L for control with SNP, and 44 mmol/L for diabetic and 0.4 mmol/L for control with carbachol). SOD signi®cantly enhanced both SNP-and carbachol-mediated diabetic cavernosal smooth muscle relaxations (both P<0.05). EFS-mediated relaxations were also signi®cantly (P<0.05) impaired in the diabetic cavernosal smooth muscle strips; these relaxations were also signi®cantly (P<0.05) enhanced by SOD. Conclusion NO-and EFS-mediated cavernosal smooth muscle relaxation is impaired in a rabbit model of diabetes but SOD signi®cantly reversed the impaired relaxation. Therefore, in diabetes, the generation of reactive oxygen species may play an important role in the development of erectile dysfunction.