Abstract
Patients with spinal cord injury (SCI) usually develop lower urinary tract dysfunctions,
including detrusor overactivity which is also known to be a risk factor for upper
urinary tract dysfunction. Antimuscarinic agents, such as propiverine, have been used
clinically for the treatment of detrusor overactivity. Also, propiverine has been
known to possess antagonistic activity against L-type Ca2+ channels and transient receptor potential vanilloid subtype 1 (TRPV1), in addition
to activity against muscarinic receptors. These mechanisms of action may contribute
to improving detrusor overactivity in SCI. We therefore investigated the effects of
antagonists of these mechanisms on non-voiding contraction (NVC) in SCI rats that
are similar to clinical cases of detrusor overactivity, and considered whether these
action mechanisms contribute to the incidence of NVC in SCI. Cystometry was performed
in rats 4 weeks after spinal transection. Urinary functions were evaluated before
and after intravenous administration of propiverine and specific antagonists for muscarinic
receptors (atropine), L-type Ca2+ channels (verapamil), and TRPV1 (capsazepine). Propiverine markedly decreased the
amplitude pressure of NVC in SCI rats, which was partially inhibited by atropine.
Verapamil also suppressed the amplitude pressure of NVC to the same degree as propiverine.
NVC disappeared almost completely after C-fiber desensitization, although capsazepine
exerted no evident effects. These findings suggest that muscarinic receptors, L-type
Ca2+ channels, and C-fiber afferent nerves contribute to the incidence of detrusor overactivity
in SCI, and a drug that has multiple antagonistic effects, such as propiverine, is
very effective for the treatment of lower urinary tract dysfunctions in SCI.
Key words
urogenital pharmacology - drug research - acetylcholine - ca-channels - transient
receptor potential channels (TRP)
