Angiotensin II and bladder obstruction in the rat: influence on hypertrophic growth and contractility.
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.
Persson
K
K
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Pandita
R K
RK
Waldeck
K
K
Andersson
K E
KE
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D005260:Female; D006984:Hypertrophy; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D009119:Muscle Contraction; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D001748:Urinary Bladder Neck Obstruction / Q000473:pathology* / Q000503:physiopathology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan