Purinergic modulation of human corpus cavernosum relaxation.

The activation of P2Y(6) receptors has been previously reported to cause vascular smooth muscle constriction and relaxation. The aim of our study was to determine the effect of P2Y(6) receptor subtype activation on human cavernosal function. Cavernosal tissue was obtained from 23 patients undergoing gender reassignment surgery. Immunohistochemistry (IHC) and Western blotting were used to determine the presence of P2Y(6) receptors in corpus cavernosal tissue. The effects of UDP (a selective P2Y(6) receptor agonist) before and after the addition of distilled water (control), cibacron blue 3GA (CB, a P2Y(6) receptor antagonist; 10(-4) m) or N-nitro-L-arginine methyl esther (L-NAME, a NO synthase inhibitor; 10(-4) m) were assessed on phenylephrine (PE; 10(-4) m) pre-contracted cavernosal strips using organ baths. Electrical field stimulation (EFS; 0.5-32 Hz) was performed in the absence and presence of CB to determine neuronal-mediated P2Y(6) receptor responses. IHC and Western blotting revealed the presence of P2Y(6) receptors on cavernosal sections. UDP at 10(-4) m and 10(-3) m induced a 5% and 16% relaxation of the PE-mediated response (both p < 0.0001), respectively, which was significantly blocked by CB (48% reduction of the UDP 10(-3) m response, p < 0.002) but not affected by L-NAME. EFS-induced relaxations of pre-contraction strips were not significantly altered by CB. We have found the presence of P2Y(6) receptors in human cavernosal tissues, that when activated induce cavernosal smooth muscle cell relaxation via non-neuronal and non-nitric oxide dependent mechanism. Further investigation is needed to establish whether P2Y(6) receptors play a physiological role in penile erection.

In vitro and in vivo effects of vardenafil (a PDE-5 Inhibitor) on corpus cavernosal smooth muscle relaxation in diabetic rabbits.

INTRODUCTION: Diabetes mellitus is associated with impaired cavernosal smooth muscle relaxation (CSMR) and the development of erectile dysfunction (ED). Vardenafil, a phosphodiesterase type 5 inhibitor has been used to treat ED. The aim of this study was to assess the in vitro and in vivo effects of vardenafil on diabetic rabbit CSMR. METHODS: Organ bath studies were used. RESULTS: Sodium nitroprusside (SNP)- and electrical field stimulation (EFS)-induced CSMR in diabetic rabbits given the vehicle was significantly impaired when compared with controls. The in vitro addition of vardenafil significantly enhanced SNP-induced CSMR in diabetic animals given the vehicle. SNP-induced CSMR in diabetic animals given in vivo vardenafil was significantly increased when compared with the diabetic untreated group. The in vitro addition of vardenafil significantly enhanced SNP and EFS-induced CSMR in cavernosal tissue taken from diabetic animals given vardenafil in vivo. CONCLUSIONS: The present findings suggest that the combination of in vitro and in vivo vardenafil enhance diabetic CSMR, reinforcing the use of vardenafil for the treatment of diabetes-induced ED.

Changes in cholinergic and purinergic neurotransmission in the diabetic rabbit bladder.

BACKGROUND: Diabetes mellitus (DM)-associated alterations in bladder function have been attributed to changes in autonomic receptors and alterations in detrusor structure and function. The changes in cholinergic and purinergic neurotransmission in the DM rabbit bladder were evaluated. MATERIALS AND METHODS: DM was induced with alloxan in adult male New Zealand White rabbits. At 6 months, detrusor and bladder neck muscle strips were obtained and mounted in organ baths. Transmural electrical field stimulation (EFS: supramaximal voltage, 0.1 ms duration, 10 s trains) was performed in the presence of atropine (10(-6) M) or alpha, beta-methylene ATP (10(-6) M), and after adding tetrodotoxin10(-6) M. Purinergic, alpha, beta-methylene ATP-sensitive, and cholinergic, atropine-sensitive, components were calculated independently and compared with those from controls. RESULTS: Both normal and DM detrusor and bladder neck strips contracted in a frequency-dependent fashion in response to transmural EFS. A plot of EFS vs. detrusor contractility showed a decrease (ANOVA < 0.001) in the cholinergic nerve-mediated component, whereas the purinergic nerve-mediated component was increased (ANOVA < 0.001) in the DM detrusor compared to the control. The total EFS- and KCl-induced responses were unaltered in the DM group compared to the controls. There was no difference in purinergic, alpha, beta-methylene ATP-sensitive, and cholinergic, atropine-sensitive, components in strips from the bladder neck for both normal and DM rabbits. CONCLUSION: These results suggest that an enhancement of purinergic and a reduction of cholinergic neurotransmission occur in the detrusor muscle of the diabetic rabbit. These changes may contribute to the pathophysiology of diabetic cystopathy.