EFFECTS OF PREGNANCY AND PROGESTERONE ON AUTONOMIC FUNCTION IN THE RAT URINARY-BLADDER

Previous studies have shown that pregnancy is associated with a decrea se in cholinergic function in the rabbit urinary bladder. The present study aimed at evaluating the effects of pregnancy on the autonomic fu nction of the rat urinary bladder and to elucidate whether progesteron e is responsible for such alterations. Female Wistar rats, 3 months ol d, were divided into four groups: (1) 2-week pregnant rats; (2) rats g iven daily intramuscular injection of progesterone 5 mg/kg for 2 weeks ; (3) rats given intramuscular injections of vehicle for 2 weeks, and (4) controls. Cystometry showed a significant increase in bladder capa city in the pregnant rats. The wet weight of the pregnant rat bladder was also significantly increased. Histologic study revealed increased bladder wall thickness with interstitial edema and urothelium prolifer ative changes to a papillary configuration in these pregnant bladders. Bladder muscle strip study showed significantly reduced maximum contr actile responses to acetylcholine and methoxamine in the pregnant and the progesterone groups. Muscarinic receptor binding study demonstrate d reduced B-max in the pregnant rats and rats receiving progesterone i njections (control group B-max = 57 +/- 11, pregnant group B-max = 44 +/- 8, p < 0.05; progesterone group B-max = 40 +/- 7, vehicle group B- max = 58 +/- 9 fmol/mg protein, p < 0.05). The contractile response to lower concentrations (10(-6) mol/l to 10(-4) mol/l) of ATP was elevat ed in the pregnant rats. It is concluded that: (1)suppressed bladder c ontractility during pregnancy is due to reduction in cholinergic and l ess importantly in alpha-adrenergic function of the organ, (2) the red uced cholinergic responsiveness is caused by decreased muscarinic rece ptor density; (3) the bladder affinity for ATP is increased during pre gnancy, and (4) exogenous progesterone administration mimicks some but not all of the pregnancy effect.