Neural Factors Controlling Urethral Outlet Activity in vivo: Role of Nitric Oxide and beta-Adrenergic System in Urethral Relaxation

Jeon, Byeong Kyu; Lee, Jeong Gu

Abstract

AIMS OF STUDY: During reflex micturition, the urethral outlet remains open (relaxed) to promote urinary emptying. The mechanisms involved in the relaxation of urethral outlet is thought to be complex including nitric oxide (NO) pathway and beta-adrenergic activity. The aims of the study focused on these several issues related to the neural control of urethral outlet in vivo. MATERIALS & METHODS: Female rats weighing 200~300 gm were anesthetized wish urethane. Catheters were inserted into femoral artery for drug administration.4 two-way catheter (16 G angiocath) was inserted into the bladder for saline infusion and pressure monitoring. A separate cannula (PE 50) was placed into the urethra via external urethral meatus or proximal urethrat opening to record urethral pressure. The bladder was filled with saline at a rate of 0.1 ml/min to induce reflex micturition. Urethral pressure was recorded via cannula through which saline was infused at a rate of 0.05 ml/min. Isovolumetric bladder contraction and urethral pressure were recorded simultaneously. After an equilibration period of 30 minutes, baseline intravesical and urethral pressure were recorded for 10 minutes prior to drug administration. NG-nitro-L-arginine methylester (L-NAME, 10 to 15 mg/kilrogram, i.v.), L-arginine (150 mg/kilrogram, i.v.), propranolol (1 microM., 0.1 ml/250 mg, i.a.), and phenylephrine (1 0~100 microM, i.a.) were administrated.
RESULTS
During isovolumetric bladder contraction, urethral pressure was decreased simultaneously, and then returned to the resting states in conjunction with end of the bladder contraction. After the administration of L-NAME, the magnitude of reflex urethral relaxation was decreased significantly (42.6 +/- 15.1% of the control, p<0.01), and this effect was reversed by addition of L-arginine. Administration of propranolol also inhibited urethral relaxation (66.4% of the control). Administration of L-NAME followed by propranolol almost completely abolished the urethral relaxation. Administration of phenylephrine increased the resting urethral tone (mean; 4 cmH2O) significantly, and the magnitude of urethral relaxation was decreased substantially.
CONCLUSION
These RESULTS suggest that urethral relaxation is mediated by several neural factors. NO seems like to a potent mediator in a reflex relaxation of the urethral smooth muscle during micturition. Also, beta-adrenergic stimulation play an important role for urethral relaxation. alpha-adrenergic nerve discharge, contributed to contraction of urethral smooth muscle, shows inhibitory effect against the reflex urethral relaxation.