Liu S P, Horan P, Levin R M
Department of Biological Science, Albany College of Pharmacy, the Stratton VA Medical Center, New York 12208, USA.
J Urol. 1998 Nov;160(5):1863-6.
In the rabbit, both cholinergic and purinergic nerves mediate bladder contraction. Acetylcholine is the neurohumoral transmitter for the cholinergic nerves, and ATP is the neurohumoral transmitter for purinergic innervation. Beta-adrenergic stimulation mediates relaxation of the bladder. In the current study, we investigated the effects of atropine, isoproterenol and propranolol on the bladder contraction induced by intra-arterial administration of acetylcholine and ATP.
Mature male New Zealand White rabbits were used in this study. A polyethylene catheter with an outer diameter of 0.043 inches was inserted through the rabbit's right femoral artery until it reached the lower abdominal aorta. An 8 F catheter was inserted through the urethral orifice into the bladder and secured by tying a 2-0 silk ligature around the bladder neck. The catheter was connected to an infusion pump and a pressure transducer by a 3-way valve. After 15 ml. of saline was infused into the bladder, an intra-arterial administration of acetylcholine and ATP was infused and the change of intravesical pressure was quantitated and recorded with a Grass model 7D polygraph. The procedure was repeated after a 5-minute pretreatment with atropine, isoproterenol or propranolol.
The results are summarized as follows: 1) Baseline intravesical pressure was not altered by pretreatment with atropine. Pretreatment with atropine shifted the dose-response curve of acetylcholine to the right and the maximal response was reduced by 9%, 49% and 77% respectively with pretreatment with atropine 10(-8), 10(-7) and 10(-6) mole/kg. The dose-response curve of ATP was not significantly affected by pretreatment with atropine. 2) Baseline intravesical pressure was lowered by pretreatment with isoproterenol. Pretreatment with isoproterenol shifted both dose-response curves of acetylcholine and ATP rightward. The maximal response of acetylcholine was reduced by 10%, 26% and 37% respectively, and the maximal response of ATP was reduced by 6%, 31% and 43% respectively by pretreatment with isoproterenol 10(-8), 10(-7) and 10(-6) mole/kg. 3) Baseline intravesical pressure was not changed by pretreatment with propranolol. Both dose-response curves of acetylcholine and ATP were not significantly affected by pretreatment with propranolol.
In conclusion, pretreatment with atropine inhibited acetylcholine-induced bladder contraction, but had no effect on ATP-induced contraction. Pretreatment with isoproterenol significantly inhibited both contractile stimulation by acetylcholine and ATP. Pretreatment with beta-adrenergic antagonist had no effect on the bladder contraction induced either by acetylcholine or by ATP. Thus, although beta-adrenergic stimulation is capable of significantly inhibiting the contractile responses to both cholinergic and purinergic stimulation, under normal conditions, sympathetic nerves do not modulate either cholinergic or purinergic stimulation.
在兔体内，胆碱能神经和嘌呤能神经均介导膀胱收缩。乙酰胆碱是胆碱能神经的神经体液递质，而三磷酸腺苷（ATP）是嘌呤能神经支配的神经体液递质。β-肾上腺素能刺激介导膀胱舒张。在本研究中，我们研究了阿托品、异丙肾上腺素和普萘洛尔对动脉内注射乙酰胆碱和ATP所诱导的膀胱收缩的影响。
本研究使用成年雄性新西兰白兔。将一根外径为0.043英寸的聚乙烯导管经兔右股动脉插入，直至到达腹主动脉下部。将一根8F导管经尿道口插入膀胱，并通过在膀胱颈周围系一根2-0丝线结扎固定。该导管通过一个三通阀连接到输液泵和压力传感器。向膀胱内注入15ml生理盐水后，动脉内注射乙酰胆碱和ATP，并使用Grass 7D型多导生理记录仪定量记录膀胱内压的变化。在用阿托品、异丙肾上腺素或普萘洛尔进行5分钟预处理后重复该过程。
结果总结如下：1）阿托品预处理未改变基线膀胱内压。阿托品预处理使乙酰胆碱的剂量-反应曲线右移，用10(-8)、10(-7)和l0(-6)摩尔/千克阿托品预处理后，最大反应分别降低了9%、49%和77%。ATP的剂量-反应曲线未受阿托品预处理的显著影响。2）异丙肾上腺素预处理降低了基线膀胱内压。异丙肾上腺素预处理使乙酰胆碱和ATP的剂量-反应曲线均右移。用10(-8)、10(-7)和10(-6)摩尔/千克异丙肾上腺素预处理后，乙酰胆碱的最大反应分别降低了10%、26%和37%，ATP的最大反应分别降低了6%、31%和43%。3）普萘洛尔预处理未改变基线膀胱内压。乙酰胆碱和ATP的剂量-反应曲线均未受普萘洛尔预处理的显著影响。
总之，阿托品预处理抑制了乙酰胆碱诱导的膀胱收缩，但对ATP诱导的收缩无影响。异丙肾上腺素预处理显著抑制了乙酰胆碱和ATP引起的收缩刺激。β-肾上腺素能拮抗剂预处理对乙酰胆碱或ATP诱导的膀胱收缩均无影响。因此，尽管β-肾上腺素能刺激能够显著抑制对胆碱能和嘌呤能刺激的收缩反应，但在正常情况下，交感神经并不调节胆碱能或嘌呤能刺激。
