ALTERED CONTRACTILITY OF URINARY-BLADDER IN DIABETIC RABBITS - RELATIONSHIP TO REDUCED NA+ PUMP ACTIVITY

We studied the effect of alloxan-induced diabetes on Na+ pump activity in isolated rabbit bladder strips. In addition, the effects of diabet es and the Na+ pump inhibitor ouabain on contractions induced by carba chol (CCh) and KCl were studied. In bladder strips from diabetic rabbi ts, ouabain-sensitive Rb-86(+) uptake (a measure of Na+ pump activity) was similar to 50% less compared with strips from normal bladder. Dia betes also reduced the maximum contractions induced by CCh and KCl. Tr eatment of bladder strips with ouabain alone caused an acute concentra tion-dependent increase in tone. In contrast, longer incubation with o uabain inhibited CCh- and KCl-induced contractions in normal and diabe tic bladders. Furthermore, differences in agonist-mediated contraction s observed between normal and diabetic bladders were abolished in the presence of the maximally effective concentration of ouabain (10 mu M) . The ability of CCh to cause contraction in normal and diabetic rabbi t bladders was also significantly inhibited by the Na+ ionophore monen sin but not by the Ca2+ ionophore A-23187 or by depolarization with KC l. Monensin also inhibited KCl-induced contractions in normal bladder strips. These results indicate that 1) Na+ pump activity is an importa nt modulator of bladder smooth muscle tone, 2) diabetes diminishes Na pump activity and inhibits agonist-induced contractions in bladder, a nd 3) an increase in intracellular Na+ concentration, secondary to inh ibition of bladder smooth muscle Na+ pump activity, is associated with reduced responsiveness to contractile agonists. Diminished Na+ pump a ctivity in diabetes may, in part, contribute to the development of bla dder cystopathy.