Relaxant effects of isoproterenol and selective beta3-adrenoceptor agonists on normal, low compliant and hyperreflexic human bladders.
OBJECTIVE
We compared the relaxant effects of the stimulation of beta-adrenoceptors with isoproterenol and of drugs selective for beta-adrenoceptor subtypes in detrusor preparations from patients with normal and neurogenic bladder, respectively.


METHODS
We studied in vitro preparations of a cystometrically normal, low compliant and hyperreflexic bladder from 45, 26 and 7 patients, respectively.


RESULTS
Isoproterenol relaxed concentration dependently and with the same potency as detrusor preparations obtained from normal and neurogenic bladders. In 37 normal detrusor, 25 low compliant and 7 hyperreflexic cases pD2 values were 6.36, 6. 25 and 6.38, respectively. Maximal relaxation did not differ significantly among the 3 groups (about 80% of 10-5 M. forskolin induced relaxation). Neither the beta1-/beta2-adrenoceptor agonist dobutamine nor the beta2-adrenoceptor agonist procaterol produced any significant relaxation of preparations from the 3 groups at a concentration of up to 10-5 M. At a concentration of 10-4 M. the preparations were relaxed but neither of these effects reached a maximum. BRL37344A and CL316243, selective beta3-adrenoceptor agonists and CGP-12177A (a selective beta3-adrenoceptor partial agonist and beta1-/beta2-adrenoceptor antagonist) relaxed detrusor preparations from the normal, low compliant and hyperreflexic groups when applied at concentrations greater than 10-6 M. For each agonist the pD2 value did not differ significantly among the 3 groups.


CONCLUSIONS
beta-adrenoceptor stimulation is an effective way of relaxing the human detrusor and the effect is similar in normal and neurogenic bladders. A major portion of the relaxant effect of isoproterenol is mediated via beta3-adrenoceptor stimulation. Clinical trials may reveal whether this method is useful for treating bladder overactivity.
Igawa
Y
Y
Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
Yamazaki
Y
Y
Takeda
H
H
Kaidoh
K
K
Akahane
M
M
Ajisawa
Y
Y
Yoneyama
T
T
Nishizawa
O
O
Andersson
K E
KE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D001750:Urinary Bladder, Neurogenic / Q000503:physiopathology*
D000318:Adrenergic beta-Agonists; D007545:Isoproterenol