Effects of a vitamin D3 analogue in a rat model of bladder outlet obstruction

Abstract

To explore the effect of the vitamin D3 analogue, BXL-628, on some of the consequences of bladder outlet obstruction (BOO), e.g. hypertrophy and loss of contractile function, as vitamin D3 and BXL-628 inhibit prostate and bladder cell growth in vitro, and there are receptors for vitamin D in rat and human bladder. In female rats, BOO was produced by a standardized method; one group received daily BXL-628 (150 microg/kg per day) and the remaining rats received vehicle. Sham-operated rats received BXL-628 or vehicle. After 2 weeks, the conscious rats were assessed by cystometry. Plasma calcium levels were determined and in vitro contractility assessed at the end of the experiments. There was a significant increase in bladder weight, micturition interval and volume, and in bladder capacity in both the obstructed groups compared to sham controls, but no difference between the obstructed groups. On plotting the micturition pressure against bladder weight within the obstructed groups, there was a clear correlation in the vehicle-treated group, indicating a decrease in contractile function with increasing bladder weight. There was no such correlation in the treatment group. In vitro, there was a strong correlation of increasing bladder weights vs decrease in response to KCl and electrical-field stimulation in strips from obstructed vehicle-treated rats, but no correlation in those from drug-treated rats. Treatment increased the plasma calcium level by 12%. The vitamin D(3) analogue used did not prevent bladder hypertrophy, but appeared to reduce some of the negative functional changes of the bladder smooth muscle, which occurs with BOO-induced increases in bladder weight.