Increased contractile response to phenylephrine in detrusor of patients with bladder outlet obstruction: effect of the alpha1A and alpha1D-adrenergic receptor antagonist tamsulosin.
OBJECTIVE
Alpha1-adrenergic receptor (alpha1-AR) antagonists are effective for treating patients with lower urinary tract symptoms associated with bladder outlet obstruction (BOO). In humans up-regulation of alpha1-AR function in the detrusor in patients with BOO has been suggested but to our knowledge it is not yet confirmed. We investigated the effect of phenylephrine, an alpha1-AR agonist, on isometric tension in small detrusor muscle biopsies from patients with lower urinary tract symptoms and BOO compared with controls.


METHODS
Detrusor biopsies were obtained from 7 men with BOO undergoing prostatectomy and 7 undergoing cystectomy for bladder cancer (controls). Patients were characterized by symptom score and urodynamics. Isometric tension was measured in detrusor biopsies with an especially built mini myograph.


RESULTS
Mean International Prostate Symptom Score +/- SEM in patients with BOO and controls were 22.3 +/- 2.3 and 4.0 +/- 0.8, respectively. Phenylephrine (10(-6) to 10(-3) M) induced a significant contractile response increase in detrusor biopsies from patients with BOO compared with controls at all concentrations. Tamsulosin (0.1 to 3.0 nM) inhibited phenylephrine induced contraction in a dose dependent manner.


CONCLUSIONS
To our knowledge this functional study shows for the first time a highly significant increase in contractile force to phenylephrine in patients with BOO compared with controls. These results suggest up-regulation of alpha1-AR function in BOO since contractile responses were potently inhibited by the alpha1A/D-AR antagonist tamsulosin.
Bouchelouche
Kirsten
K
Smooth Muscle Laboratory, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Andersen
Lisa
L
Alvarez
Susana
S
Nordling
Joergen
J
Bouchelouche
Pierre
P
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D000077409:Tamsulosin; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000503:physiopathology*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D013449:Sulfonamides; D010656:Phenylephrine; D000077409:Tamsulosin