The effect of indomethacin on the muscarinic induced contractions in the isolated normal guinea pig urinary bladder

Abstract

Background: To investigate the effect of prostaglandin depletion by means of COX-inhibition on cholinergic enhanced spontaneous contractions. Methods. The urethra and bladder of 9 male guinea pigs (weight 270-300 g) were removed and placed in an organ bath with Krebs' solution. A catheter was passed through the urethra through which the intravesical pressure was measured. The muscarinic agonist arecaidine, the non-selective COX inhibitor indomethacin, and PGE§ssub§2§esub§ were subsequently added to the organ bath. The initial average frequency and amplitude of spontaneous contractions in the first 2 minutes after arecaidine application were labelled F§ssub§ ini§esub§ and P§ssub§ini§esub§, respectively. The steady state frequency (F§ssub§steady§esub§) and amplitude (P§ssub§steady§esub§) were defined as the average frequency and amplitude during the 5 minutes before the next wash out. Results: Application of 1 μM PGE§ssub§2§esub§ increased the amplitude of spontaneous contractions without affecting frequency. 10 μM of indomethacin reduced amplitude but not frequency.The addition of indomethacin did not alter F§ssub§ini§esub§ after the first application (p = 0.7665). However, after the second wash, F§ssub§ini§ esub§ was decreased (p = 0.0005). F§ssub§steady§esub§, P§ssub§steady§esub§ and P§ssub§ini§esub§ were not significantly different in any of the conditions. These effects of indomethacin were reversible by PGE§ssub§2§esub§ addition.§ssub§.§esub§. Conclusions: Blocking PG synthesis decreased the cholinergically stimulated autonomous contractions in the isolated bladder. This suggests that PG could modify normal cholinergically evoked response. A combination of drugs inhibiting muscarinic receptors and PG function or production can then become an interesting focus of research on a treatment for overactive bladder syndrome. © 2013 Rahnama'i et al.; licensee BioMed Central Ltd.