Angiotensin ii and bladder obstruction in the rat: influence on
hypertrophic growth and contractility.
Persson, Katarina, Raj Kumar Pandita, Kristian Waldeck, and Karl-Erik
Andersson.
Department of Clinical Pharmacology, Lund University Hospital, S
-221 85 Lund, Sweden
APStracts 3:0198R, 1996.
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 (15mg/kg/day) 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 to
sham rats. However, no difference was observed in bladder weight or
bladder protein content between losartan-treated rats and rats
receiving no drug. Cystometrical 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 when compared to 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
of Ang II (1[mu]M) that amounted to 4.4+/-1.0% of the response to K+
(124mM). The Ang II-induced contraction was abolished by losartan
(10[mu]M) and indomethacin (10[mu]M). The contractile response to Ang
II (1[mu]M), K+ (124mM) and transmural nerve stimulation (2Hz) 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 mediated by stimulation of the AT1 subtype
receptor.
Received 25 September 1995; accepted in final form 6 May 1996.
APS Manuscript Number R606-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96