Effect of ZD6169, a K+ Channel Opener, on Bladder Tissue of Rat with Bladder Outlet Partial Obstruction

Park, Yang Il; Park, Sung Hun; Min, Kyung Dae; Kwon, Dong Deuk

Abstract

It has been established that ZD6169 is a unique ATP-sensitive potassium channel opener with in vivo selectivity of relaxing bladder smooth muscle and may be useful in treatment of bladder instability associated with minimal hemodynamic side effects. We evaluated microcsopical changes of bladder wall of rats received oral ZD6169 with partial bladder outlet obstruction. Female, conscious Sprague-Dawley rats (300-350g) were randomly divided into three groups; I: control group (n=5), II: partial bladder obstruction group (n=10), III: partial bladder obstruction group receving orally ZD6169 (n=10). ZD6169 was given orally, three times per week for two weeks. Then all bladders were harvested, weighed and fixed, and embedded for light microscopy. We examined the microscopocal structure of the bladder musculature. Mean bladder weight in both group II and III was significant greater than in group I, and The increase in group II was more marked than in group III (p<0.05). The light microscope shows that the detrusor muscle contains numerous fiber bundle loosely arraneged in connective tissue in group I. In contrast, the detrusor muscle fibers in group II were densely arragened with connective tissue, markedly different from group I. The change of detrusor muscle in group III was similar to that of group I. These results demonstrated that the detrusor muscle of rats treated orally ZD6169 revealed, the ultrastructural finding similar to that of the control rats. ZD6169 is sufficient to suppress smooth muscle contraction and may represent a novel, promising way of treating bladder overactivity.