Changes to the contractile function of ureter smooth muscle after partial infravesical obstruction in fetal sheep

Abstract

To measure spontaneous contractile activity, and the responses to agonists using in vitro preparations of sheep ureter after a period of bladder outlet obstruction (BOO) initiated at mid-gestation. Date-mated Romney Marsh ewes, bearing fetuses of 70-75 days of gestation (term in this breed is 145 days) were used. Five fetuses underwent urachal obstruction and partial urethral constriction for 30 days. Six fetuses at the same gestational time underwent a sham operation (control group). Small strips of mid-ureter were cut in the longitudinal axis, and in the cross-sectional (transverse) plane of the ureter. Spontaneous contractile activity and the response to carbachol, high-K(+) (120 mM) solution and alpha,beta-methylene ATP (ABMA) were characterized by measuring the magnitude of evoked responses and the magnitude and frequency of spontaneous activity. The ureters from fetuses with BOO were significantly larger in diameter and had expanded lumens. The proportion of smooth muscle was not significantly different between the BOO and control groups. Spontaneous contractile activity in all preparations was resistant to atropine and the neurotoxin, tetrodotoxin. With transverse sections, the magnitude of spontaneous contractions was smaller in the BOO group, but the frequency was greater. The response to carbachol was also smaller in the BOO group, but the response to high-K(+) solution was similar to that of the control group. ABMA did not generate a response in any preparation. With longitudinal ureteric preparations, spontaneous or agonist-induced activity was negligible in the control group, while preparations from the BOO sheep had spontaneous activity and responded to carbachol and high-K(+) solutions. These results show that in fetuses with BOO and dilated ureters absolute ureteric contractile activity is diminished. However, there is functional reorganization of the muscle layers that generates more force in the longitudinal rather than the transverse axis. This would contribute to a reduced ability of the ureter to propel urine and contribute to the development of raised upper tract pressures.