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 diabetes and the Na+ pump inhibitor ouabain on contractions induced by carbachol (CCh) and KCl were studied. In bladder strips from diabetic rabbits, ouabain-sensitive 86Rb+ uptake (a measure of Na+ pump activity) was approximately 50% less compared with strips from normal bladder. Diabetes also reduced the 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 microM). 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 A-23187 or by depolarization with KCl. Monensin also inhibited KCl-induced contractions in normal bladder strips. These results indicate that 1) Na+ pump activity is an important modulator of bladder smooth muscle tone, 2) diabetes diminishes Na+ pump activity and inhibits agonist-induced contractions in bladder, and 3) 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.
Gupta
S
S
Department of Urology, Boston University School of Medicine, Massachusetts 02118, USA.
Yang
S
S
Cohen
R A
RA
Krane
R J
RJ
Saenz De Tejada
I
I
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D001743:Urinary Bladder / Q000503:physiopathology*
D000254:Sodium-Potassium-Exchanging ATPase