Effect of KW-7158, a putative afferent nerve inhibitor, on bladder and vesico-vascular reflexes in rats

The effects of KW-7158, a putative afferent nerve inhibitor, on reflex bladder activity and vesico-vascular reflexes were evaluated in urethane anesthetized SD rats with normal and xylene-irritated bladders. The bladder was filled with saline until the appearance of large amplitude spontaneous bladder contractions (LA-BC). Vesico-vascular reflexes were measured as increases in systolic arterial blood pressure during LA-BC or when the bladder was distended by a range of pressures. In normal rats, KW-7158 (10 and 100 mug/kg, i.v.) did not alter the amplitude or volume threshold for inducing LA-BC but increased the intercontraction interval. After xylene-irritation, which decreased volume threshold and intercontraction interval and induced small amplitude bladder contractions, KW-7158 increased volume threshold (65%) and intercontraction interval (150%) and decreased the number of small amplitude bladder contractions. Vesico-vascular reflexes induced during LA-BC or by bladder distension were suppressed (19.4-100%) by KW-7158. The effect of KW-7158 to depress vesico-vascular reflexes as well as xylene-induced bladder hyperactivity without altering the amplitude of contractions is consistent with the view that the drug affects reflex bladder activity at least in part by depressing afferent pathways. (C) 2002 Elsevier Science B.V. All rights reserved.