The actions of sodium nitroprusside and the phosphodiesterase inhibitor dipyridamole on phasic activity in the isolated guinea-pig bladder.
OBJECTIVE
To investigate the actions of the nitric oxide (NO) donor sodium nitroprusside (SNP) and phosphodiesterase (PDE) inhibitors, which purport to affect intracellular cGMP levels, on the phasic activity generated by agonist stimulation of the isolated whole bladder of the guinea pig.


METHODS
Isolated whole bladders from female guinea pigs (270-300 g) were used in all experiments. Each bladder was cannulated via the urethra and suspended in a chamber containing oxygenated solution at 33-35 degrees C. Bladder pressure was recorded and pharmacological agents added to the solution bathing the abluminal surface of the bladder.


RESULTS
In the unstimulated bladder, SNP at up to 300 micromol/L caused only small (<2 cmH(2)O) rises in intravesical pressure. In the presence of phasic activity induced by either muscarinic or nicotinic stimulation, SNP at > 30 micromol/L, produced a dose-dependent increase in the frequency of the transients. The cells responding to SNP with an increase in intracellular cGMP were identified by immunofluorescence, and were in the suburothelial layer and within the muscle bundles. Smooth muscle cells of the detrusor body did not show a rise in cGMP. Exposure to the cGMP/PDE inhibitor zaprinast had no effect on phasic activity, but exposure to dipyridamole produced a transient rise in frequency, followed by an inhibition. Dipyridamole also significantly increased the amplitude of the phasic activity.


CONCLUSIONS
These data show an excitatory role for NO/cGMP in the integrated regulation of phasic bladder activity. One population of cells which may be involved may be in the suburothelial layer and within the muscles. The differential sensitivity to PDE inhibitors affecting cGMP suggests that the cells responsible express specific isoforms of these regulatory enzymes. The importance of these observations, their possible role in the integrated physiology of the bladder and origins of bladder pathology, are discussed.
Gillespie
J I
JI
The Urophysiology Research Group, School of Surgical and Reproductive Sciences, The Medical School, The University, Newcastle upon Tyne NE2 4HH, UK. j.i.gillespie@ncl.ac.uk
Drake
M J
MJ
D000818:Animals; D006152:Cyclic GMP / Q000172:deficiency; D004176:Dipyridamole / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011312:Pressure; D001743:Urinary Bladder / Q000187:drug effects*
D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D009599:Nitroprusside; D004176:Dipyridamole; D006152:Cyclic GMP