ANGIOTENSIN-II AND BLADDER OBSTRUCTION IN THE RAT - INFLUENCE ON HYPERTROPHIC GROWTH AND CONTRACTILITY

The mechanisms and mediators of hypertrophic growth secondary to infra vesical urinary outflow obstruction are unknown. The renin-angiotensin system has been implicated in vascular and cardiac hypertrophy, but t he involvement of angiotensin II (ANG II) as a trophic factor in the l ower urinary tract has not been investigated. In this study, the ANG I I subtype AT(1) receptor antagonist losartan (DuP 753) was administere d perorally (15 mg . kg(-1). day(-1)) for 28 days to rats subjected to partial urethral obstruction or sham surgery. Partial urethral obstru ction caused a 3.5-fold increase in bladder weight and a 3-fold increa se in bladder protein content compared with sham rats. However, no dif ference was observed in bladder weight or bladder protein content betw een losartan-treated rats and rats receiving no drug. Cystometric eval uation of bladder function revealed significant increases in micturiti on volume, bladder capacity, bladder compliance, and spontaneous contr actile activity in rats subjected to partial urethral obstruction comp ared with sham rats. However, bladder function in rats treated with lo sartan was not different fi om bladder function in rats receiving no d rug. In vitro studies of isolated bladder tissue showed a weak contrac tile response to ANG II (1 mu M) that amounted to 4.4 +/- 1.0% of the response to K+ (124 mM). The ANG II-induced contraction was abolished by losartan (10 mu M) and indomethacin (10 mu M). The contractile resp onse to ANG II (1 mu M), K+ (124 mM), and transmural nerve stimulation (2 Hz) was reduced in bladder strips from obstructed rats. In conclus ion, no evidence was found for involvement of ANG II in development of bladder hypertrophy. The effect of ANG II on bladder smooth muscle to ne was minor but was mediated by stimulation of the AT(1) subtype rece ptor.