The role of alpha1-adrenoceptor and arachidonate pathways in increased tone of demucosalized bladder tissue.
OBJECTIVE
We investigated the role of the alpha1-adrenoceptor system, and cyclooxygenase and lipoxygenase pathways in increased contractile reactivity of demucosalized bladder tissues.


METHODS
A total of 20 male Sprague-Dawley rats were used. From each bladder 2 tissue strips were prepared. One strip was demucosalized, while the other was kept intact. Isometric tension studies were done at baseline tone with contractile responses assessed to 120 mM potassium, electrical field stimulation (1 to 40 Hz) and carbachol (10(-9) to 10(-4) M). Relaxation responses to electrical field stimulation, isoproterenol (10(-9) to 10(-4) M), papaverine (10(-4) M) and sodium nitroprusside (10(-4) M) were recorded in carbachol precontracted strips. The effects of doxazosin, the cyclooxygenase inhibitor indomethacin and the lipoxygenase inhibitor REV5901 (each 3 x 10(-5) M) on these responses were investigated.


RESULTS
Carbachol and electrical field stimulation induced significantly greater contractions in demucosalized strips. All contractile responses were significantly decreased in the presence of doxazosin, indomethacin and REV5901 in intact and demucosalized tissues. Indomethacin augmented the effect of doxazosin on demucosalized tissue contractions compared to results obtained with doxazosin alone. In carbachol precontracted tissues relaxation responses to isoproterenol and electrical field stimulation were significantly lower in demucosalized tissues. These responses were significantly decreased with doxazosin or indomethacin independent of mucosa.


CONCLUSIONS
Bladder mucosa is a determinant of rat bladder tissue contractility. Doxazosin, and cyclooxygenase and lipoxygenase pathways significantly affect rat bladder tissue contractility independent of mucosa. However, the effect of doxazosin is significantly amplified by cyclooxygenase inhibition in the absence of bladder mucosa. These findings may have important clinical implications regarding the single and combined use of doxazosin with cyclooxygenase inhibitors.
Tarcan
Tufan
T
Department of Urology, Marmara University School of Medicine, Istanbul, Turkey. tufan@marmara.edu.tr
Ozdemir
Ilker
I
Onol
Fikret Fatih
FF
D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009092:Mucous Membrane / Q000601:surgery; D009119:Muscle Contraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D015398:Signal Transduction; D001743:Urinary Bladder / Q000502:physiology* / Q000601:surgery
D018340:Receptors, Adrenergic, alpha-1; D016718:Arachidonic Acid