Intravesical protamine sulfate and potassium chloride as a model for bladder hyperactivity.
OBJECTIVE
An acute animal model for hyperactive bladder in rats was developed using intravesical infusion of protamine sulfate (PS), an agent thought to break down urothelial barrier function, and physiologic concentrations of potassium chloride (KCl).


METHODS
Continuous cystometrograms (CMGs) were performed in urethane-anesthetized female rats by filling the bladder (0.04 mL/min) with normal saline followed by intravesical infusion of a test solution consisting of either KCl (100 or 500 mM) or PS (10 or 30 mg/mL) for 60 minutes. Subsequently, the 10 mg/mL PS-treated animals were infused intravesically with 100, 300, or 500 mM KCl. Some animals were pretreated with capsaicin (125 mg/kg subcutaneously) 4 days before the experiments.


RESULTS
Unlike KCl (100 or 500 mM) or a low concentration of PS (10 mg/mL) alone, the intravesical administration of a high concentration of PS (30 mg/mL) produced irritative effects with a decreased intercontraction interval (by 80.6%). After infusion of a low concentration of PS, infusion of 300 or 500 mM KCl produced irritative effects (intercontraction interval decreased by 76.9% or 82.9%, respectively). The onset of irritation occurred more rapidly after 500 mM KCl (10 to 15 minutes) than after 300 mM KCl (20 to 30 minutes). Capsaicin pretreatment delayed the onset (approximately 60 minutes) and reduced the magnitude (intercontraction interval decreased by 35.5%) of irritative effects.


CONCLUSIONS
Intravesical administration of KCl after PS treatment activates capsaicin-sensitive afferents and detrusor muscle and presumably capsaicin-resistant afferents. Modest, noncytotoxic affronts to urothelial barrier function can result in dramatic irritative responses. This model may be useful in the study of bladder irritation and hyperactivity.
Chuang
Yao-Chi
YC
Division of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Chancellor
Michael B
MB
Seki
Satoshi
S
Yoshimura
Naoki
N
Tyagi
Pradeep
P
Huang
Leaf
L
Lavelle
John P
JP
De Groat
William C
WC
Fraser
Matthew O
MO
D000283:Administration, Intravesical; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology; D018856:Cystitis, Interstitial / Q000139:chemically induced* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D011189:Potassium Chloride / Q000008:administration & dosage* / Q000494:pharmacology; D011479:Protamines / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D014554:Urination / Q000187:drug effects
D011479:Protamines; D011189:Potassium Chloride; D002211:Capsaicin