[PDE5 inhibitors. A new option in the treatment of ureteral colic?].
BACKGROUND
PDE5 inhibitors represent the gold standard in the medical therapy of erectile dysfunction (ED). Promising results have been published regarding further urological indications such as treatment of ureteral colic. The aim of the present study was to evaluate the functional effects of the PDE5 inhibitors sildenafil (SIL), vardenafil (VAR), and tadalafil (TAD) on tissue tension and cyclic nucleotide levels of human ureteral smooth muscle segments in vitro.


METHODS
Relaxant responses of human ureteral smooth muscle were investigated in vitro using the organ bath technique. Cyclic nucleotides cAMP and cGMP were determined by specific radioimmunoassays.


RESULTS
Relaxing effects of ureteral muscle tension were observed in the rank order VAR>SIL>TAD. While only VAR significantly elevated cGMP levels 3.3-fold over control, no increase for cAMP levels was observed.


CONCLUSIONS
Our data provide evidence that cGMP is involved in the control of the normal function of the smooth musculature of the human ureter. Our findings suggest the potential of using selective inhibitors of PDE isoenzymes in the treatment of ureteral colic.
Gratzke
C
C
Klinik und Poliklinik für Urologie, Ludwig-Maximilians-Universität, München. christian.gratzke@med.uni-muenchen.de
Uckert
S
S
Reich
O
O
Schlenker
B
B
Tilki
D
D
Seitz
M
M
Stief
C G
CG
D000368:Aged; D002243:Carbolines / Q000627:therapeutic use; D003085:Colic / Q000188:drug therapy* / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D009924:Organ Culture Techniques; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use; D011687:Purines / Q000627:therapeutic use; D011863:Radioimmunoassay; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use; D000068581:Tadalafil; D014227:Triazines / Q000627:therapeutic use; D014513:Ureter / Q000187:drug effects / Q000473:pathology; D014514:Ureteral Calculi / Q000188:drug therapy / Q000473:pathology; D014515:Ureteral Diseases / Q000188:drug therapy* / Q000473:pathology; D000069058:Vardenafil Dihydrochloride
D002243:Carbolines; D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000068581:Tadalafil; D000068677:Sildenafil Citrate; D000242:Cyclic AMP; D006152:Cyclic GMP