Effect of tetracyclines and 4-epiderivatives on the ureter

1. The effect of tetracyclines on the isolated dog ureter is dependent on: (a) the tetracyclines used-mepicycline and doxycycline antagonizing, and tetracycline and rolitetracycline increasing the contractor action of barium chloride; (b) the percentage of 4-epiderivatives in the tetracyclines used-the higher the epiderivative concentration, the smaller the effect of mepicycline or doxycycline, and the greater the action of tetracycline or rolitetracycline.2. In vivo the addition of the antibiotics into the renal pelvis shows no significant differences between the various tetracyclines or different 4-epiderivative concentrations on the intra-ureteral flow of the dog or guinea-pig.3. Intravenous injection of mepicycline or doxycycline does not induce a significant change in the intra-ureteral flow, while intravenous administration of tetracycline or rolitetracycline produces a triphasic response: (a) a marked decrease of the intra-ureteral flow for a few minutes; (b) a return to the control condition for 30-60 min; and (c) a lesser but persistent decrease in flow for 60-120 minutes. In the first phase the ureteral smooth muscle is directly affected by the antibiotics circulating in the blood, while in the third phase the tetracyclines act via the intra-ureteral mucosa.4. Neurogenic effects on the ureter-bladder junction in vivo are not affected by the tetracyclines tested.