AN ELECTROMYOGRAPHIC STUDY OF THE FELINE URETHRAL RHABDOSPHINCTER IN THE NORMAL STATE AND AFTER SACRAL RHIZOTOMY Part 2. Responses of the Rhabdosphinc

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1 AN ELECTROMYOGRAPHIC STUDY OF THE FELINE URETHRAL RHABDOSPHINCTER IN THE NORMAL STATE AND AFTER SACRAL RHIZOTOMY Part 2. Responses of the Rhabdosphincter to Hypogastric Nerve Stimulation Hidehiro Kakizaki Department of Urology, Hokkaido University School of Medicine (Director: Prof. T. Koyanagi) To investigate functional aspect of sympathetic innervation of the urethral rhabdosphincter, responses of the male feline rhabdosphincter to hypogastric nerve (HGN) were examined by means of electromyography using fine electrodes. Experiments were performed on 28 normal (N group) and 13 rhizotomized cats under chloralose anesthesia, the latter being further divided into two groups: 4 cats of 1-3 weeks (SR group) and 9 cats of weeks (LR group) after complete sacral rhizotomy. HGN (1Hz, 0.3ms pulse duration, 2-30 V) elicited responses of the rhabdosphincter in N and LR groups. In N group, HGN still elicited responses of the rhabdosphincter even after pudendal nerve was transected in advance, indicating that these evoked potentials were independent of somatic nerve inflow. The threshold stimuli and latencies of the evoked responses in N group ( V, ms, respectively) were not significantly different from those in LR group ( V, ms), but the amplitudes of the evoked responses were significantly larger in LR group than in N group ( vs 18+2V, p<0.001). These evoked responses of the rhabdosphincter were resistive to prazosin (0.2mg/kg) and atropine (0.5mg/kg), but were abolished by hexamethonium (2mg/min, 10-25mg) and pancuronium ( mg/kg) in both groups. In N group; repetitive (10-20Hz) of HGN increased activities of the rhabdosphincter when the bladder was empty, but not when the bladder was full enough to trigger the vesicourethral relaxation reflex. This excitatory effect of HGN on activities of the rhabdosphincter in the empty bladder was blocked by prazosin. After administration of prazosin, HGN inhibited the increased activities of the rhabdosphincter induced by the urethrourethral contraction reflex. This inhibitory effect was blocked by propranolol. These data suggest that 1) in both normal and chronically rhizotomized cats, HGN-evoked responses of the rhabdosphincer are induced through a pathway involving HGN and cholinergic postganglionic neurons which act on nicotinic receptors of the rhabdosphincter. 2) sympathetic preganglionic input to this cholinergic postganglionic synapse is present normally, 3) after complete sacral rhizotomy, sympathetic preganglionic neurons develop wider contact with decentralized cholinergic postganglionic neurons and cholinergic postganglionic terminals form more effective functional connections to somaticallydenervated end-plates of the rhabdosphincter, and 4) in normal cats, HGN modulates activities of stretch receptors in the urethral wall through contraction or relaxation of urethral smooth muscle. Key words: feline rhabdosphincter electromyography, sacral rhizotomy, hypogastric nerve

3 Table 1 Threshold stimuli, latency and amplitude of hypogastric nerve-evoked potentials of the rhabdosphincter, and effects of various blockades on the evoked potentials Fig. 2 Hypogastric nerve-evoked responses and spontaneous motor unit potentials of the rhabdosphincter in normal cat. Arrows, arrowheads and asterisks indicate stimulus artifacts, evoked responses and spontaneous discharges of motor units, respectively. Values are mean+se. Number of experiments in parentheses. *Significantly different from N group (p<0.001). Fig. 1 Hypogastric nerve-evoked EMG activities of the rhabdosphincter in normal cat. Upward arrows indicate the onset of hypogastric nerve. Fig. 3 Effect of various blockades on hypogastric nerve-evoked responses of the rhabdosphincter in normal cat.

4 Fig. 4 Hypogastric nerve-evoked multiple responses of the rhabdosphincter (upper trace) in chronically rhizotomized cat. Lower trace shows only spontaneous discharges of the rhabdosphincter. Fig. 5 Effect of various blockades on hypogastric nerve-evoked responses of the rhabdosphincter in chronically rhizotomized cat. The potentials are photographed on recording films. nerve-evoked responses of the rhabdosphincter in chronically rhizotomized cat. The potentials are recorded on moving paper. Fig. 6 Effect of various blockades on hypogastric

5 1089 Fig. 7 Action ral contraction tric nerve potentials reflex induced (upper (lower Table by vesicoureth- trace) and hypogas- trace). 2 Effect of prazosin of repetitive frequency of action cter in normal Effect of repetitive ulation on activities normal cat. hypogastric of the nerve stim- rhabdosphincter in nerve potentials influence on of the rhabdosphin- cats Values are mean+se. entheses. *Significantly Fig. 8 on excitatory hypogastric Number different ** Not significantly of experiments in par- from before stim. (p<0.02). different from before stim. (p> ). Fig. 9 Effect of prazosin of repetitive hypogastric normal on excitatory nerve influence cat. は下腹神経に頻回刺激を加えても膀胱内圧む変化は観察されなかった. 刺激前後の活動電位の頻度を比較すると(Table2), は2.4±0.8 分, 1 2分 24.3±7.5, 刺激前1分 spikes/secで間の活動電位む平均頻度あったが, 刺激終了後0 1 では活動電位む平均頻度はそれぞれ 23.4±5.5 spikes/secとなり, 刺激前に比べ約10倍の頻度を呈した.膀胱を充満させ, 膀胱一尿 Fig. 10 cter Increased induced are nerve (upper effect is blocked by propranolol Note は, 下腹神経に刺激を加えても外尿道括約筋に活動電 artifacts. 8). 次に膀胱空虚時の下腹神経刺激による外尿道括約筋活動の増強効果に対するプラゾシソの影響を検討した. プラゾシソを投与しておき, 20分後に下腹神経に刺激を加えて外尿道括約筋の活動電位の頻度を検討すると, 刺激前1分び刺激終了後0 1分, 1 2分度はそれぞれ0.4±0.1, 1.7±0.9, 間およむ活動電位む平均頻 0.5±0.1 spikes/ secであり, 下腹神経刺激による外尿道括約筋活動む増強効果はプラゾシンにより抑制された(Table2, Fig.9). of the urethrourethral reflex 道弛緩反射により外尿道括約筋が弛緩した状態下で位は記録されなかった(Fig. activities by that suppressed the EMG by traces rhabdosphincontraction repetitive trace). hypogastric This include inhibitory (lower trace). the stimulus in

6 Fig. 11 Effect of various blockades on repetitive hypogastric nerve -evoked responses of the rhabdosphincter in chronically rhizotomized cat.

9 1) Elbadawi, A, and Schenk, E.: A new theory of the innervation of the bladder musculature. IV. Innervation of the vesicourethral junction and external urethral sphincter. J. Urol., 111, , 1974, 2) Elbadawa, A. and Atta, M.A.: Ultrastructure of vesicourethral innervation. IV. Evidence for somatomotor plus autonomic innervation of the male feline rhabdosphincter. Neurourol. Urodyn., 4, 23-36, 1985, 3) Elbadawi, A, and Atta, M.A.: Intrinsic neuromuscular defects in the neurogenic bladder. V. Autonomic re-innervation of the male feline rhabdosphincter following somatic denervation by bilateral sacral ventral rhizotomy. Neurourol. Urodyn., 5, 63-85, 1986, 4) Atta, M.A, and Elbadawi, A.: Intrinsic neuromuscular defects in the neurogenic bladder. IV. Loss of somatomotor and preservation of autonomic innervation of the male feline rhabdosphincter following bilateral sacral ventral rhizotomy. Neurourol. Urodyn., 4, , ) Flood, H.D., Downie, J.W. and Awad, S.A.: Urethral function after chronic cauda equina lesion in cats. II. The role of autonomicallyinnervated smooth and striated muscle in distal sphincterdysfunction. J. Urol., 144, , ) Gajewski, J., Downie, J.W. and Awad, S.A.: Experimental evidence for a central nervous system site of action in the effect of alphaadrenergic blockers on the external urinary sphincter. J. Urol., 133, , ) Sundin, T, and Dahlstrom, A.: The sympathetic innervation of the urinary bladder and urethra in the normal state and after parasympathetic denervation at the spinal root level. Scand. J. Urol. Nephrol., 7, , ) Slack, B.E. and Downie, J.W.: Pharmacological analysis of the responses of the feline urethra to autonomic nerve. J. Auton. Nerv. Syst., 8, , ) Gosling, J.A., Dixon, J.S., Critchley, H.O.D. and Thompson, S.A.: A comparative study of the human external sphincter and periurethral levator ani muscles. Brit. J. Urol., 53, 35-41, ) Nishizawa, O., Fukuda, T., Matsuzaki, A., Moriya, I., Harada, T. and Tsuchida, S.: Role of the sympathetic nerve in bladder and urethral sphincter function during the micturition cycle in the dog evaluated by pressure flow EMG study. J. Urol., 134, , ) de Groat, W.C. and Kawatani, M.: Reorganization of sympathetic preganglionic connections in cat bladder ganglia following parasympathetic denervation. J. Physiol., 409, , 1989

ALPHA ADRENERGIC MECHANISM ON THE REFLEX MICTURITION IN THE MALE DECEREBRATE DOG Tokuo Takahashi Department of Urology, Akita University School of Med

ALPHA ADRENERGIC MECHANISM ON THE REFLEX MICTURITION IN THE MALE DECEREBRATE DOG Tokuo Takahashi Department of Urology, Akita University School of Medicine (Director: Prof. Seigi Tsuchida) We investigated