Different effect of anticholinergic agents and potassium channel openers on urinary bladder response to pelvic nerve stimulation in anaesthetized dogs.
1. Effects of the anticholinergic agents atropine, oxybutynin, and terodiline, and the potassium channel openers YM934 (2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl) pyridine N-oxide) and cromakalim were examined on urinary bladder response to pelvic nerve stimulation in pentobarbital-anaesthetized dogs. 2. Pelvic nerve stimulation (PNS) produced a frequency-dependent increase in intravesical pressure in anaesthetized dogs. The response to PNS was abolished by topical tetrodotoxin, and markedly inhibited by intravenous hexamethonium, suggesting a neurogenic origin for the in vivo contractile response. 3. Atropine (0.3-3 mg kg-1 i.v.) and the anti-neurogenic bladder agents, oxybutynin (1-10 mg kg-1 i.v.) and terodiline (1-10 mg kg-1 i.v.) dose-dependently decreased the amplitude of the peak intravesical pressure response to PNS. At either frequency of PNS, these agents inhibited the response to a similar degree. 4. The potassium channel openers YM934 (1-10 micrograms kg-1 i.v.) and cromakalim (3-30 micrograms kg-1 i.v.) dose-dependently decreased the amplitude of the peak intravesical pressure response to PNS. The inhibitory effects of these drugs were more potent at lower than at higher frequencies of PNS. 5. These data suggest that the inhibitory effects of potassium channel openers on urinary bladder response to PNS are different from those of anticholinergic agents. The preferential inhibitory effect of potassium channel openers on detrusor smooth muscle contraction at lower frequencies of PNS may represent new potential for the treatment of neurogenic bladder.
Sudoh
K
K
Pharmacology Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Masuda
N
N
Uchida
W
W
D000758:Anesthesia; D000818:Animals; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D010525:Peripheral Nerves / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000502:physiology*
D018680:Cholinergic Antagonists; D015221:Potassium Channels; D018738:Hexamethonium