Intravesical oxyhemoglobin initiates bladder overactivity in conscious, normal rats.
OBJECTIVE
To investigate whether intravesical oxyhemoglobin, a nitric oxide scavenger, changes bladder activity in normal rats.


METHODS
Oxyhemoglobin was given intravesically at different concentrations to conscious, female Sprague-Dawley rats undergoing continuous cystometry.


RESULTS
Intravesical oxyhemoglobin increased bladder activity in a concentration-dependent way. At a concentration of 2.5 x 10-4 M (n = 8), micturition pressure (p <0. 01), basal pressure (p <0.01), and residual volume (p <0.05) increased, and bladder capacity (p <0.001) and micturition volume (p <0.001) decreased. The effect of oxyhemoglobin was reduced or abolished by L-arginine (200 mg./kg.-1), given intra-arterially near the bladder, and was enhanced by the guanylate cyclase inhibitor, ODQ (0.5 and 1 mg./kg.-1). The K+ channel opener, ZD6169 100 ng.ml. -1, given intravesically for 1 hour prior to instillation of oxyhemoglobin, reduced or completely prevented the bladder activity induced by oxyhemoglobin.


CONCLUSIONS
Intravesical oxyhemoglobin induces bladder overactivity, probably by interfering with nitric oxide (NO) generated in the urothelium or suburothelially. NO may be involved in the regulation of the threshold for afferent firing in the bladder.
Pandita
R K
RK
Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden.
Mizusawa
H
H
Andersson
K E
KE
D000283:Administration, Intravesical; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001577:Benzophenones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000008:administration & dosage*; D015221:Potassium Channels / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D014554:Urination / Q000187:drug effects; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000577:Amides; D001577:Benzophenones; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D010069:Oxadiazoles; D010108:Oxyhemoglobins; D015221:Potassium Channels; D011810:Quinoxalines; C095007:Zeneca ZD 6169; D009569:Nitric Oxide; D001120:Arginine; D006162:Guanylate Cyclase