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Electrophysiological techniques were used to examine the asynchronous and evoked activity on postganglionic nerves to the urinary bladder in the urethananesthetized rat. Distension of the bladder (0.4-0.6 ml) evoked reflex contractions of the bladder (mean intravesical pressure 28 cmH2O) and efferent firing on postganglionic nerves. Electrical stimulation of afferent and efferent axons in the pelvic nerve elicited short-latency (0.3-11 ms) responses and long-latency (45-170 ms) reflexes on the nerves. The short-latency responses consisted of nonsynaptic axonal volleys with conduction velocities ranging from 0.5 to 11 m/s and synaptic responses with latencies of 6-11 ms. Stimulation of the pelvic nerve elicited late supraspinal reflexes (mean latency 122 +/- 28 ms) in 60% of normal rats and an early reflex (mean latency 56 +/- 5 ms) in 25% of those animals in which a late reflex was also identified. Early reflexes (mean latency 50 +/- 9 ms) were elicited in 100% of chronic spinal animals. The conduction time for the afferent and efferent limbs of the reflexes was calculated to be 7 and 58 ms, respectively, with a central delay of 57 ms for the late and less than 5 ms for the early reflex. It is concluded that sacral parasympathetic input to the urinary bladder of the rat is mediated by supraspinal and spinal reflex pathways. It is likely that in normal animals the late-occurring supraspinal reflex mediates micturition. The significance of the spinal reflex in the normal animals is uncertain; however, this reflex is essential for the generation of automatic micturition in chronic spinal preparations.

Partial urethral ligation in female Wistar rats produces changes in the neural control of the lower urinary tract including bladder hyperactivity and facilitation of a spinal micturition reflex pathway. To gain insight into the mechanisms underlying these changes, axonal tracing studies were conducted to examine the postganglionic efferent limb of the micturition reflex pathway which originates in the major pelvic ganglion (MPG). Forty microliters of the tracer Fluoro-Gold (4%) were injected into the right side of the bladder in urethral-obstructed (n = 10) and control (n = 4) rats 6 weeks after urethral ligation or sham surgery. As a control Fast blue (40 microliters, 5%) was injected into the colon to label neurons in the MPG innervating the intestine. Obstructed rats exhibited a 6-fold increase (p less than 0.001) in bladder weight (0.848 gm) compared to controls (0.148 gm). A significant increase (p less than 0.001) in the size of labeled bladder postganglionic neurons in the MPG was noted in obstructed rats (576.4 microns 2, n = 4) as compared to controls (299.6 microns 2). However, labeled, colon postganglionic neurons in the MPG in obstructed (312.9 microns 2) rats were not enlarged compared to controls (359.4 microns 2). Neuronal hypertrophy was not associated with a change in the number of labeled MPG neurons in control and obstructed groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term efficacy and safety of sildenafil was assessed in 1008 patients with erectile dysfunction (ED) enrolled in four flexible-dose (25 -100 mg), open-label, 36-or 52-week extension studies. After 36 and 52 weeks, 92% and 89% of patients felt that treatment with sildenafil had improved their erections. Responses to a Sexual Function Questionnaire indicated that 52 weeks of sildenafil treatment resulted in clinically significant improvements in the duration and firmness of erections, overall satisfaction with sex life, and the frequency of stimulated erections. Commonly reported adverse events (AEs) were headache, flushing, dyspepsia, and rhinitis, which were generally mild to moderate. Reports of abnormal vision were consistent with previous clinical trials. The occurrence of treatment-related cardiovascular AEs, such as hypertension, tachycardia, and palpitation, was < 1%. Discontinuations due to treatment-related AEs were low (2%). Long-term therapy does not diminish the efficacy of sildenafil in patients with ED and remains well tolerated.