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Intravesical oxyhemoglobin initiates bladder overactivity in conscious, normal rats
R K Pandita1, H Mizusawa, K E Andersson
1Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden.
Purpose:
To investigate whether intravesical oxyhemoglobin, a nitric oxide scavenger, changes bladder activity in normal rats.
Materials And 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.