Urothelium-dependent and urothelium-independent detrusor contractility mediated by nitric oxide synthase and cyclooxygenase inhibition.
OBJECTIVE
The urothelium has been implicated in regulating detrusor smooth muscle contractility but the identity of the putative urothelium-derived inhibitory factor remains unconfirmed. There was inconclusive evidence on the role of nitric oxide synthase (NOS) and cyclooxygenase (COX) in mediating detrusor contractions. This study examined varying regulation by NOS and COX in transverse and longitudinal carbachol (CCh)-induced and unstimulated phasic contractions.


METHODS
Rat detrusor strips with the urothelium-intact (+UE) and urothelium-denuded (-UE) were isolated in both transverse and longitudinal directions. Isometric tension of the detrusor strips was recorded both during stimulation with CCh and at the unstimulated state. In the unstimulated state, phasic contractile activity was measured. Tension recordings were made with and without the NOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) and COX inhibitor indomethacin (Indo).


RESULTS
Only transverse +UE strips responded convincingly to L-NAME and Indo treatment, generating larger CCh-induced contractions. In unstimulated tissues, L-NAME treatment increased phasic amplitude in -UE strips only. Indo treatment failed to elicit any change in the amplitude but suppressed frequency of the phasic activity in transverse +UE strips. There was no significant Indo-mediated change in other strips.


CONCLUSIONS
The data suggested heterogeneity in the regulation of directional detrusor contractility via NOS- and COX-associated mechanisms.
School of Biological Sciences, College of Science, Nanyang Technological University, Singapore, Singapore.
Aneira Gracia Hidayat
AG
Santoso
Wan Ning
WN
Lo
Willmann
W
Liang
D000704:Analysis of Variance; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology; D019459:Urothelium / Q000187:drug effects / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin