Up-regulation of endothelin-B (ETB) receptors and ETB receptor-mediated rabbit detrusor contraction in partial bladder outlet obstruction

Objective To investigate, in a rabbit model of bladder outlet obstruction (BOO), whether ET(B) receptors initiate any contractile activity, and to assess the density of these receptors. Materials and methods Partial BOO was produced in male New Zealand White rabbits, with age-matched sham-operated rabbits acting as controls. One and 3 weeks later, the detrusor and bladder neck strips were incubated in organ baths with either BQ788 tan ET(B) antagonist), BQ123 fan ET(A) antagonist) or vehicle. Concentration-response curves were constructed using IRL-1620 (a selective ET(B) agonist). Low-resolution autoradiography was performed on serial detrusor and bladder neck sections from control and partial BOO (3-week) rabbits using radioligands for ET(A) and ET(B). Results In strips from controls and after 1 week of partial BOG. IRL-1620 induced no contractions, but after 3 weeks of BOG, IRL-1620 induced significant concentration-dependent detrusor contractions (producing 12%, 25% and 70% of the I(CI response at 10(-8), 10(-7) and 10(-6) mol/L, respectively). The ET(A) antagonist had no effect on IRL-1620-mediated contractions. In contrast, the ET(B) antagonist completely abolished these contractions. Autoradiography showed the presence of ET(A) and ET(B) receptors in the detrusor and bladder neck of normal and obstructed animals, and a significant up-regulation of ET(A) and ET(B) receptors only in the obstructed detrusor smooth muscle. Conclusions In BOG, ET(B) receptors initiate detrusor contractile activity. This is a time-dependent process that may depend on the up-regulation of ET(B) receptors in the detrusor. Therefore, ET(B) receptors may play a role in the pathophysiology of partial BOG.