Temporal changes in rabbit urinary bladder function and DNA synthesis during chronic treatment with furosemide.

In a preliminary study we showed that 14 days of furosemide infusion in rabbits caused increases in bladder mass and contractile responses of bladder body strips to field stimulation, bethanechol, ATP and KCl. The present study investigated the temporal effects of furosemide-induced diuresis on micturition, bladder mass, bladder wall proliferation activity and DNA synthesis. In addition, contractile responses of bladder body strips were monitored. Furosemide-containing osmotic pumps were implanted in male New Zealand White rabbits. Micturition was monitored for 7 days. Biochemical analyses were done 3, 7 and 14 days after implantation. Contractile responses were measured at 3 and 7 days. Polyuria and polydipsia started within 1 day after implantation of furosemide-containing osmotic pumps and continued at the same level for 7 days. Bladder mass was significantly increased at 3 and 7 days. Diuresis stimulated 3H-thymidine uptake and caused an increase in bladder DNA concentration at 3 days. However, both DNA concentrations and 3H-thymidine levels returned to control levels by 7 days. Contractile responses to field stimulation and agonists were increased at 7 days but unchanged at 3 days. The data confirm that modest increases in bladder mass and the ensuing increases in contractile function are a normal and beneficial physiological response to diuresis.