vasoactive-intestinal-peptide and Urethral-Obstruction

Nitric oxide (NO) has been proposed to function as an inhibitory neurotransmitter in the lower urinary tract. This study investigates the distribution of NO-containing neurons and its changes following urethral obstruction in the guinea-pig. By using nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and NO synthase (NOS) immunohistochemistry, the highest frequency of NO-containing neurons was observed in the bladder base. Double labelling studies showed that 70.9% of NADPH-d reactive neurons co-expressed NOS immunoreactivity. Acetylcholinesterase reactivity was present in the majority of the intramural neurons with 54% of them expressed NOS immunoreactivity. NADPH-d reactivity was colocalized with vasoactive intestinal polypeptide, calcitonin gene-related peptide and substance P immunoreactivities in both neurons and fibres. Colocalization study also revealed that NADPH-d reactive neurons formed a distinct cell population from tyrosine hydroxylase positive neurons. At 12 hours after urethral obstruction, NADPH-d reactivity in the intramural ganglion cells was noticeably enhanced and this was sustained till 24 hours whence some intensely stained neurons appeared to undergo degenerative changes. Neuronal degeneration was more drastic at 48 hours so that the number of NADPH-d positive neurons was significantly reduced. The present study suggests that NO is an important neurotransmitter in the urinary bladder and that it may be involved in the relaxation activity in the bladder base during micturition. It is speculated that the increased NADPH-d reactivity in intramural ganglion cells elicited by urethral obstruction may be responsible for the cell death. It is suggested that the resulting cell loss or bladder denervation may account for the urinary dysfunction such as frequency and urgency of micturition in patients with urethral obstruction.

Topics: Acetylcholinesterase; Animals; Calcitonin Gene-Related Peptide; Ganglia; Guinea Pigs; Histocytochemistry; Immunohistochemistry; Male; NADPH Dehydrogenase; Neurons; Neurotransmitter Agents; Nitric Oxide Synthase; Substance P; Time Factors; Urethral Obstruction; Urinary Bladder; Vasoactive Intestinal Peptide

The concentrations of substance P and vasoactive intestinal polypeptide (VIP) were determined in the upper, middle, and lower part of the bladder of rats with and without infravesical outflow obstruction. In the obstructed animals there was a significant increase in bladder weight and the total amounts of substance P and VIP were increased. However, the concentrations of substance P were significantly lower than in the control bladders. The concentrations of VIP, on the other hand, were significantly higher in the middle and lower parts of obstructed bladders than in the controls. In isolated strips of the normal and obstructed bladders VIP had neither contractile nor relaxant effects. The peptide had no effect on electrically induced contractions. Substance P produced concentration-dependent contractions in both normal and obstructed bladders. However, obstructed bladders were significantly less sensitive than controls. It is concluded that the bladder instability seen in rats with infravesical outflow obstruction cannot be explained only in terms of changes in the bladder content of substance P or VIP.

Topics: Animals; Female; Rats; Rats, Inbred Strains; Substance P; Urethra; Urethral Obstruction; Urinary Bladder; Vasoactive Intestinal Peptide