THE EFFECT OF THE SPECIFIC PHOSPHODIESTERASE-IV-INHIBITOR ROLIPRAM ONTHE URETERAL PERISTALSIS OF THE RABBIT IN-VITRO AND IN-VIVO

Purpose: Cyclic nucleotide phosphodiesterases (PDE's) are intracellula r key enzymes in the regulation of the tone in smooth muscle cells. Th ere are 5 different isoenzyme families that show a specific organ and species distribution pattern; The aim of our study was to examine poss ible selective ureteral relaxation by the specific PDE-IV-inhibitor ro lipram in the rabbit. Materials and Methods: For in vitro studies uret ers 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 sys temic blood pressure were continuously monitored 40 minutes before and at least 60 minutes after injection of the drugs. Results: Scopolamin e had no effect on ureteral peristalsis, but significant effects on sy stemic blood pressure were observed. Papaverine and theophylline showe d short-lasting ureteral relaxations, but were accompanied by severe c irculatory side effects. Rolipram showed pronounced ureteral relaxatio n with minimal circulatory effects. Conclusion: Our results show that intravenous administration of the specific PDE-IV-inhibitor rolipram r elaxes the rabbit ureter without significant circulatory side effects. Because human and rabbit ureter show similar relaxation results in vi tro, this pharmacological approach seems promising for the treatment o f ureteral colic and the facilitation of urinary stone passage in huma ns.