Effects of intravenous and infravesical administration of suramin, terazosin and BMY 7378 on bladder instability in conscious rats with bladder outlet obstruction.
OBJECTIVE
To evaluate the effect of the nonselective purinergic antagonist suramin and the alpha1-adrenergic antagonists, terazosin and BMY 7378, given intravenously or infused directly into the bladder during cystometry in conscious rats with bladder outlet obstruction induced by urethral ligation.


METHODS
Cystometry was performed in conscious female rats recording bladder volume capacity (BVC), evaluated as the amount of saline infused between two voiding cycles, and micturition volume (MV). Changes in frequency and amplitude of spontaneous non-voiding bladder contractions (NVC) were also recorded. The effects of the intravenous administration of suramin (100 mg/kg), BMY 7378 (1 mg/kg), and terazosin (0.3 mg/kg) on NVC, BVC and MV were evaluated in obstructed rats with bladder infusion of saline. The effects of infravesical infusion of suramin (3-10 micromol/L), terazosin (1 micromol/L) and BMY 7378 (10 micromol/L) were also evaluated and compared with values observed in control rats during saline infusion into the bladder.


RESULTS
Intravenous injection with suramin had no effects on NVC, BVC and MV, but suramin infused into the bladder induced a consistent reduction in the amplitude of NVC (significantly different from matched control animals) with a tendency to reduce their frequency. BVC and MV were slightly but significantly decreased by infravesical infusion of suramin. In contrast, BMY 7378 and terazosin, given intravenously, were extremely potent at inhibiting the frequency and amplitude of the NVC, but were inactive on NVC when infused into bladder.


CONCLUSIONS
These findings confirm a role for alpha1-adrenergic receptors in bladder instability caused by bladder outlet obstruction. In addition, a purinergic neurotransmitter, presumably ATP, is shown to be involved.
Velasco
C
C
Pharmaceutical R&D Division, Recordati SpA, Milano, Italy. Velasco.c@recordati.it
Guarneri
L
L
Leonardi
A
A
Testa
R
R
D000283:Administration, Intravesical; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D000818:Animals; D005260:Female; D007262:Infusions, Intravenous; D008026:Ligation; D010879:Piperazines / Q000008:administration & dosage; D011224:Prazosin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058914:Purinergic Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D013498:Suramin / Q000008:administration & dosage; D014524:Urethral Obstruction / Q000188:drug therapy; D001748:Urinary Bladder Neck Obstruction / Q000150:complications* / Q000503:physiopathology; D014554:Urination / Q000187:drug effects; D014555:Urination Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014563:Urodynamics
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D058914:Purinergic Antagonists; D013498:Suramin; C041226:Terazosin; C053428:BMY 7378; D011224:Prazosin