Effects of atropine, isoproterenol and propranolol on the rabbit bladder contraction induced by intra-arterial administration of acetylcholine and ATP.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Biological Science, Albany College of Pharmacy, the Stratton VA Medical Center, New York 12208, USA.
S P
SP
Liu
P
P
Horan
R M
RM
Levin
D000109:Acetylcholine / Q000008:administration & dosage*; D000255:Adenosine Triphosphate / Q000008:administration & dosage*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007269:Injections, Intra-Arterial; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology*; D011817:Rabbits; D001743:Urinary Bladder / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018727:Muscarinic Antagonists; D001285:Atropine; D000255:Adenosine Triphosphate; D011433:Propranolol; D007545:Isoproterenol; D000109:Acetylcholine