Prostaglandins and cyclic nucleotides in the urinary bladder of a rabbit model of partial bladder outlet obstruction.
Bladder outlet obstruction (BOO) is a common disorder that is associated with altered bladder structure and function. For example, it is well established that BOO results in hypertrophy and hyperplasia of the bladder smooth muscle as well as detrusor instability. Since prostaglandins (PGs) and cyclic nucleotides (cyclic AMP [cAMP] and cyclic GMP [cGMP]) mediate both smooth muscle tone and proliferation, it is reasonable to suggest that changes in their levels may be involved in the pathophysiology of BOO-associated bladder disorders. Hence, the objective of this study was to investigate cyclic AMP, cyclic GMP and prostaglandins in the bladder of a rabbit model of BOO. BOO was induced in adult male New Zealand White rabbits. After 3 weeks, urinary bladders were excised, weighed and cut into segments. They were then incubated with stimulators of PGs, cAMP and cGMP and the formation of PGs, cAMP and cGMP were measured using radioimmunoassays. There was a significant increase in the obstructed bladder weights (P=0.002). The formation of PGE2, PGI2, cAMP and cGMP was significantly diminished in the detrusor (P<0.05) and bladder neck (P<0.05) in the BOO bladders compared to age-matched controls. Since PGE2, PGI2, cAMP and cGMP are known to inhibit the proliferation of smooth muscle cells (SMCs), the decreased synthesis of these factors, in BOO, may play a role in bladder SMC hypertrophy/hyperplasia. Our study points to the possible use of drugs that modulate the NO-cGMP and/or PG-cAMP axes in BOO-associated bladder pathology.
Khan
M A
MA
Department of Urology, Royal Free Hospital, London, UK.
Thompson
C S
CS
Angelini
G D
GD
Morgan
R J
RJ
Mikhailidis
D P
DP
Jeremy
J Y
JY
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000096:biosynthesis; D006965:Hyperplasia; D006984:Hypertrophy; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D011817:Rabbits; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism* / Q000473:pathology
D011453:Prostaglandins; D015240:Phorbol 12,13-Dibutyrate; D000001:Calcimycin; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP; D015232:Dinoprostone; D000109:Acetylcholine