Vol. 292, Issue 1, 67-75, January 2000

Effects of -Adrenergic Stimulation on the Acutely Obstructed Ureter in Dogs

Makoto Murakami, Yoshitaka Tomiyama, Kohichi Hayakawa, Masuo Akahane, Yukiyoshi Ajisawa, Young-Chol Park, Norio Ohnishi, Takahide Sugiyama and Takashi Kurita

Division of Discovery Research, Kissei Pharmaceutical Co., Ltd., Nagano (M.M., Y.T., K.H., M.A., Y.A.); and Department of Urology, Kinki University School of Medicine, Osaka, Japan (Y.-C.P., N.O., T.S., T.K.)

The objective of the present study was to evaluate the effects of a selective ₃-adrenoceptor agonist, (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316243), on the acutely obstructed ureter in anesthetized dogs. After a complete ureteral obstruction produced by the inflation of a balloon catheter placed within the left lower ureter, the intraluminal ureteral pressure gradually rose to reach a plateau of ~52.5 mm Hg. Intravenous administration of isoproterenol (a nonselective -adrenoceptor agonist; 10 µg/kg) and CL 316243 (1 µg/kg) significantly decreased this elevated ureteral pressure (by 74.1 and 77.2%, respectively), with the reduction more sustained with CL 316243 than with isoproterenol. In addition, under both isoproterenol and CL 316243, urine flow (which had been interrupted by the balloon) was resumed, resulting in further sustained decreases in ureteral pressure. The mean blood pressure decreased and heart rate increased after the administration of both drugs, but these changes were greater in the isoproterenol group than in the CL 316243 group. In contrast, i.v. administration of butylscopolamine (an anticholinergic agent; 1000 µg/kg) had no evident effects on ureteral pressure or on urine flow. The increase in left kidney weight seen after ureteral obstruction was suppressed by CL 316243. We conclude that the selective ₃-adrenoceptor agonist tested appears to be more useful than isoproterenol for reducing ureteral pressure above the obstructed site and for promoting ureteral relaxation and increasing urine flow around the point of obstruction in dogs.