THE EFFECT OF INVIVO ESTROGEN PRETREATMENT ON THE CONTRACTILE RESPONSE OF RAT ISOLATED DETRUSOR MUSCLE

1 The effect of oestradiol pretreatment was investigated on the response of rat isolated detrusor muscle to cholinergic, electrical and 5-hydroxytryptamine (5-HT) stimulation with and without diethystilboestrol (DES) (2 mum) in the organ bath. 2 Virgin female Wistar rats were injected subcutaneously for 8 days with oestradiol benzoate 150 mug kg-1. Control rats received no injections or injection only with the vehicle, ethyl oleate. 3 Detrusor muscle from treated rats showed a decreased sensitivity to acetylcholine (ACh) and carbachol-induced contractile responses. The dose-response curves to these agonists showed a 44% reduction in maximum contractile response for ACh (P < 0.001), and a 38% reduction in maximum contractile response for carbachol (P < 0.05). The addition of 2 mum DES to the bathing medium further significantly reduced the maximum contractile response by 56 and 57% of control respectively. 4 Electrically stimulated detrusor muscle from treated rats showed a significant 49% reduction in the maximum contractile response (P < 0.001). The addition of 2 mum DES to the bathing medium further significantly reduced the maximum contractile response by 66% of control. The tetrodotoxin resistant responses were smaller in pretreated rats, suggesting a reduced sensitivity of the smooth muscle to direct electrical stimulation. 5 The response to 5-HT stimulation by detrusor muscle samples from oestradiol-treated rats showed a non-significant reduction in maximum contractile response, but the addition of 2 muM DES to the bath chamber resulted in a 67% reduction in the response (P < 0.001). 6 Oestradiol pretreatment did not affect the potassium dose-response curve. 7 Oestradiol pretreatment reduced the rat detrusor muscle sensitivity to the blocking effect of atropine on the response to electrical field stimulation. Pretreatment also reduced the potentiating effect of physostigmine on the same response. 8 These results suggest that oestradiol pretreatment had a modulating effect on cholinergic responses. The addition of oestrogen to the tissue environment enhances this inhibitory effect.