Literature search and in vitro studies on ureteral function in humans
and rabbits have proven that the rabbit is a suitable animal model for
the investigation of the effect of smooth muscle relaxing substances
on the ureter. One of the main problems encountered was to find an app
ropriate anesthetic protocol for this animal model. Application of bar
biturates as a monotherapy proved to be unsuitable to allow painfree p
reparation of the abdomen. Intravenous (iv) anesthesia consisting of k
etamine-HCl/xylazine-HCl could not be considered due to interference w
ith ureteral smooth muscle tone. Intravenous administration of ketamin
e-HCl induced immediate ureteral contractions with increased frequency
of ureteral activity. Xylazine-hydrochloride, a mixed alpha(2)-, alph
a(1)-adrenoceptor agonist inhibits the increase in synthesis of 3'5'-c
AMP. Since the test substances used are phosphodiesterase-IV-inhibitor
s (rolipram and its two enantiomers), which increase 3'5'-cAMP, this t
ype of anesthesia would interfere with the pharmacological effect to b
e investigated. General anesthesia using a combination of nitrous oxid
e (2 l/min) and oxygen (1 l/min) and a very small amount (2 mg/kg b.w.
) of pentobarbital i.v. every 30 minutes, was found to be the most sui
table form of anesthesia. It resulted in much more stable circulatory
conditions, sufficient depth of anesthesia and the possibility to test
muscle relaxing substances (PDE-IV-inhibitor) without any influence f
rom anesthesia on their efficacy.