The Role of alpha 1-Adrenoceptor and Arachidonate Pathways in Increased Tone of Demucosalized Bladder Tissue

Abstract

Purpose: We investigated the role of the alpha 1-adrenoceptor system, and cyclooxygenase and lipoxygenase pathways in increased contractile reactivity of demucosalized bladder tissues. Materials and 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.