The effect of the specific phosphodiesterase-IV-inhibitor rolipram on the ureteral peristalsis of the rabbit in vitro and in vivo

Purpose: Cyclic nucleotide phosphodiesterases (PDE's) are intracellular key enzymes in the regulation of the tone in smooth muscle cells. There are 5 different isoenzyme families that show a specific organ and species distribution pattern; The aim of our study was to examine possible selective ureteral relaxation by the specific PDE-IV-inhibitor rolipram in the rabbit. Materials and Methods: For in vitro studies ureters were taken from 12 patients who underwent radical nephrectomy and from 4 rabbits which were sacrificed. For the in vivo study 23 rabbits received intravenous administration of papaverine (300 mu g./kg, b.w., n = 2), scopolamine (667 mu g./kg. b.w., n = 2), theophylline (5 mg./kg. b.w., n = 2) and rolipram (5 and 20 mu g./kg. b.w., n = 9 and n = 8). Ureteral dynamic parameters (frequency, amplitude, tonus) and systemic blood pressure were continuously monitored 40 minutes before and at least 60 minutes after injection of the drugs. Results: Scopolamine had no effect on ureteral peristalsis, but significant effects on systemic blood pressure were observed. Papaverine and theophylline showed short-lasting ureteral relaxations, but were accompanied by severe circulatory side effects. Rolipram showed pronounced ureteral relaxation with minimal circulatory effects. Conclusion: Our results show that intravenous administration of the specific PDE-IV-inhibitor rolipram relaxes the rabbit ureter without significant circulatory side effects. Because human and rabbit ureter show similar relaxation results in vitro, this pharmacological approach seems promising for the treatment of ureteral colic and the facilitation of urinary stone passage in humans.