The effect of ovariectomy and dietary phytoestrogen on contractile responses to carbachol in the rat isolated bladder

Abstract

The overall function and morphology of the bladder changes with age. Detrusor contractility, bladder capacity and time to void declines over time and can be coupled with an increase in nonvoiding contraction frequency (1). In many women the development of urinary incontinence occurs following menopause. Lower urinary tract symptoms including leakage, frequency urgency, dysuria and nocturia and are generally considered to be part of the menopausal syndrome (2). The effect of long-term consumption of dietary phytoestrogens on maintenance of bladder structure and contractility in post menopausal women remains unclear. This study examined the effect of ovariectomy and dietary phytoestrogen on muscarinic receptor mediated contractile responses in the rat isolated bladder. Female Wistar rats (8 weeks) were anaesthetised (ketamine 60 mg/kg and xylazine 8 mg/kg, IP) and an abdominal mid-ventral incision was made. The ovaries were removed (ovx) or left intact (sham), then closed and allowed to recover. Rats were fed either normal rat chow (soy, phytoestrogens) or a non-soy (phytoestrogen free) diet. At 12 or 24 wks of age rats the bladder was dissected into two sections and the segments placed in 25 ml organ baths filled with Krebs-Henseleit solution, kept at 32 0C, gassed with a 5% CO2: 95% O2 mix and placed under 1g tension. Loss of oestrogen or dietary phytoestrogens did not affect the bladder weight from rats at 12 or 24 weeks when compared within each age group (P>0.05). At 12 weeks of age, the contractile response to carbachol did not change as a result of dietary phytoestrogens or loss of oestrogen (P>0.05). However, at 24 weeks of age, the detrusor strips from non-soy ovx treated rats had reduced contractile tension with a maximal response of 4.14 ± 0.46 g (n=8) compared to age-matched non-soy sham (6.04 ± 0.87 g, n=8), soy sham (6.56 ± 1.17 g, n=8) and soy ovx (6.24 ± 0.83 g, n=8) groups (P<0.05 ). The results suggest that loss of oestrogen following ovariectomy, causes a reduction in the contractile response of the detrusor to the muscarinic receptor agonist carbachol in the female rat bladder over time. An effect that appears to be prevented by dietary phytoestrogen.

1. Michel M, Barendrecht MM (2008) Pharmacol Ther 117, 297-312 2. Nelson HD (2008) The Lancet 371(9614), 760-770