In Vitro Effects of Plasma Collected From Rats Administered Naftopidil on Whole Urinary Bladder Preparation Isolated From Rats

Abstract

Alpha-1-adrenoceptor blockers (e.g., naftopidil) are prescribed for the treatment of male lower urinary tract symptoms. Although the mechanism of action of naftopidil has been studied in various organs, that in the urinary bladder remains unknown. To clarify the direct effects of naftopidil on this organ, activities were assessed in the isolated rat whole urinary bladder. Methods: A total of 30 female rats were used. In Experiment 1, bladder activity was measured during a cumulative administration of 2.5-75μM naftopidil (n = 7). In Experiment 2, rats were divided into 2 groups: control (n = 10) and naftopidil (5 mg/ animal/day, oral gavage, once-daily for 2 weeks) (n = 13). After the treatment period, plasma was obtained from each rat. The urinary bladders were harvested from the control rats. Isovolumetric rhythmic bladder contractions were induced at above the threshold volume, and intravesical pressure was recorded. Control plasma was added to the organ bath; after subsequent wash-out, plasma collected from rats administered naftopidil was added. In Experiment 3, the plasma levels of monoamines and amino acids were quantified using the individual plasma prepared in the Experiment 2. Results: Cumulative dosing with naftopidil did not change the interval between spontaneous contractions compared to the interval at baseline. After adding control plasma, the interval was shortened compared to the baseline (P = 0.008). The plasma collected from rats administered naftopidil suppressed the shortening of the interval compared to the control plasma (P = 0.041). Naftopidil resulted in a decrease in the level of noradrenaline (P = 0.009) and an increase in that of glycine (P = 0.014). Conclusions: Although naftopidil did not directly act on the interval between spontaneous contractions of the urinary bladder, the plasma collected from rats administered naftopidil, with changing levels of monoamines and amino acids, may suppressed shortening the interval.