The mechanisms and mediators of hypertrophic growth secondary to infravesical urinary outflow obstruction are unknown. The renin-angiotensin system has been implicated in vascular and
cardiac hypertrophy, but the involvement of
angiotensin II (ANG II) as a trophic factor in the lower urinary tract has not been investigated. In this study, the ANG II subtype AT1 receptor antagonist
losartan (
DuP 753) was administered perorally (15 mg.kg-1.day-1) for 28 days to rats subjected to partial
urethral obstruction or
sham surgery. Partial
urethral obstruction caused a 3.5-fold increase in bladder weight and a 3-fold increase in bladder
protein content compared with
sham rats. However, no difference was observed in bladder weight or bladder
protein content between
losartan-treated rats and rats receiving no
drug. Cystometric evaluation of bladder function revealed significant increases in micturition volume, bladder capacity, bladder compliance, and spontaneous contractile activity in rats subjected to partial
urethral obstruction compared with
sham rats. However, bladder function in rats treated with
losartan was not different from bladder function in rats receiving no
drug. In vitro studies of isolated bladder tissue showed a weak contractile response to ANG II (1 microM) that amounted to 4.4 +/- 1.0% of the response to K+ (124 mM). The ANG II-induced contraction was abolished by
losartan (10 microM) and
indomethacin (10 microM). The contractile response to ANG II (1 microM), K+ (124 mM), and transmural nerve stimulation (2 Hz) was reduced in bladder strips from obstructed rats. In conclusion, no evidence was found for involvement of ANG II in development of bladder
hypertrophy. The effect of ANG II on bladder smooth muscle tone was minor but was mediated by stimulation of the AT1 subtype receptor.