alpha1-Adrenergic mechanism in diabetic urethral dysfunction in rats.
OBJECTIVE
We investigated the contribution of alpha1-adrenoceptor mechanisms to urethral dysfunction associated with diabetes mellitus (DM) in rats.


METHODS
Eight weeks after streptozotocin injection (65 mg/kg intraperitoneally) the effects of DM on urethral relaxation mechanisms were evaluated with subjects under urethane anesthesia by simultaneous recordings of intravesical pressure in isovolumetric conditions and urethral perfusion pressure (UPP).


RESULTS
In diabetic rats the intravesical pressure thresholds for inducing urethral relaxation and the lowest urethral pressure (UPP nadir) during urethral relaxation were significantly higher by 142% and 86%, respectively, than in normal rats, while baseline UPPs were not significantly different. The mean rate of high frequency oscillations of urethral striated muscle in diabetic rats was also significantly lower by 23% than in normal rats. After alpha-bungarotoxin treatment (333 mug/kg intravenously) to eliminate striated muscle sphincter contractions the SD of baseline UPPs was significantly larger by 93% than in normal rats. Intravenous administration of terazosin (0.4 mg/kg), an alpha1-adrenoceptor antagonist, significantly decreased the UPP nadir, intravesical pressure thresholds inducing urethral relaxation and the SD by 41%, 87% and 138%, respectively, in diabetic rats but not in normal rats. In the 2 groups of animals after alpha-bungarotoxin treatment urethral relaxation during a reflex bladder contraction was inhibited by Nomega-nitro-L-arginine (40 mg/kg intravenously), a nitric oxide synthase inhibitor.


CONCLUSIONS
During reflex bladder contractions streptozotocin induced diabetic rats showed smooth and striated muscle dysfunctions of the urethra. The inhibition of alpha1-adrenoceptors, which decreased the UPP nadir and UPP fluctuation, may be useful for treating urethral dysfunction in DM.
Torimoto
Kazumasa
K
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213-3221, USA.
Hirao
Yoshihiko
Y
Matsuyoshi
Hiroko
H
de Groat
William C
WC
Chancellor
Michael B
MB
Yoshimura
Naoki
N
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D014521:Urethra / Q000187:drug effects / Q000503:physiopathology*
D002038:Bungarotoxins; D018340:Receptors, Adrenergic, alpha-1