Relaxant effects of potassium-channel openers on normal and hyper-reflexic detrusor muscle.
OBJECTIVE
To compare the effects of the potassium-channel openers, levcromakalim and YM934, in isolated human detrusor muscle from normal and hyper-reflexic bladders.


METHODS
Strips of human detrusor muscle from normal and hyper-reflexic bladder were pre-contracted with carbachol and the potassium-channel openers (0.1-0.3 mumol/L) were added cumulatively to the organ baths. Other strips were field-stimulated at frequencies producing 25% and 75% of the maximum response to field stimulation. Contractions could be abolished by atropine (10 mumol/L) and tetrodotoxin (1 mumol/L).


RESULTS
The hyper-reflexic bladder was significantly more sensitive to carbachol than the normal bladder but the maximum response was significantly lower in the hyper-reflexic tissue. There was no significant difference between the potency of the potassium-channel openers in normal and hyper-reflexic detrusor muscle. Hyper-reflexic bladder was significantly more sensitive to electrical field stimulation than was normal bladder: maximum responses to field stimulation were not significantly different. Concentration-response curves for the potassium-channel openers were displaced to the left in hyper-reflexic bladder at both 25% and 75% maximum frequencies: however, only with levcromakalim at 75% of the maximum frequency was the shift significant.


CONCLUSIONS
The greater sensitivity of hyper-reflexic bladder to carbachol and field stimulation supports existing evidence for post-junctional supersensitivity in detrusor instability. The results of this study also suggest that there are no appreciable changes in KATP channel function in the unstable bladder.
Martin
S W
SW
Department of Biomedical Science, University of Sheffield, UK.
Radley
S C
SC
Chess-Williams
R
R
Korstanje
C
C
Chapple
C R
CR
D001578:Benzopyrans / Q000494:pharmacology*; D048588:Benzoxazines; D002217:Carbachol / Q000494:pharmacology; D019806:Cromakalim; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects*; D010078:Oxazines / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D012021:Reflex, Abnormal; D001743:Urinary Bladder / Q000502:physiology*
D001578:Benzopyrans; D048588:Benzoxazines; D003497:Cyclic N-Oxides; D010078:Oxazines; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D002217:Carbachol; C084963:2H-1,4-benzoxazine, 3,4-dihydro-2,2-dimethyl-6-nitro-4-(2-pyridinyl)-, N-oxide