Altered contractility of urinary bladder in the diabetic rabbit: relationship to reduced na + -pump activity. Gupta, Sandeep, Stone Yang, Richard A. Cohen, Robert J. Krane, and I[tilde]nigo Saenz De Tejada. DEPARTMENT OF UROLOGY AND VASCULAR BIOLOGY UNIT, BOSTON UNIVERSITY SCHOOL OF MEDICINE, BOSTON, MA 02118
APStracts 3:0267C, 1996.
We studied the effect of alloxan-induced diabetes on Na+-pump activity in isolated rabbit bladder strips. In addition, the effects of diabetes and the Na+-pump inhibitor, ouabain, on contractions induced by carbachol (Cch) and potassium chloride (KCl) were studied. In bladder strips from diabetic rabbits, ouabain-sensitive 86Rb-uptake (OS; a measure of Na+-pump activity) was approximately 50% less compared to strips from normal bladder. Diabetes also reduced maximum contractions induced by Cch and KCl. Treatment of bladder strips with ouabain alone caused an acute concentration-dependent increase in tone. In contrast, longer incubation with ouabain inhibited Cch and KCl-induced contractions in normal and diabetic bladders. Furthermore, differences in agonist-mediated contractions 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 rabbit bladders was also significantly inhibited by the Na+-ionophore, monensin, but not by the Ca2+ ionophore, A23187, or upon depolarization with KCl. Monensin also inhibited KCl-induced contractions in normal bladder strips. These results indicate that i) Na+-pump activity is an important modulator of bladder smooth muscle tone; ii) diabetes diminishes Na+-pump activity and inhibits agonist -induced contractions in bladder; iii) an increase in intracellular Na+-concentration, secondary to inhibition of bladder smooth muscle Na+-pump activity, is associated with reduced responsiveness to contractile agonists. Diminished Na+-pump activity in diabetes may, in part, contribute to the development of bladder cystopathy.

Received 9 July 1996; accepted in final form 24 May 1996.
APS Manuscript Number C289-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996