There is an increased prevalence of urinary bladder dysfunction with ageing. Although the contributing factors underlying this are unknown, it may be related to the actions of inflammatory mediators (1, 2). Treatment with histamine induces significant increases in both the tonic contractions and frequency of spontaneous phasic contractions in both urothelium with lamina propria and the underlying detrusor muscle through the activation of the H1 receptor (3). Additionally, this effect may work in conjunction with other inflammatory-cell released chemicals such as 5-HT (4) or prostaglandins (5). This study aimed to compare urothelium with lamina propria (U&LP) and detrusor responses to histamine and prostaglandin E2 in juvenile and adult tissues. Functional tissue baths containing adjacent strips of porcine U&LP or detrusor smooth muscle were mounted in gassed Krebs-bicarbonate solution at 37°C. Responses to histamine and prostaglandin E2 in the absence and presence of selective receptor antagonists were examined in juvenile and adult tissues. Data analysis of the responses was performed using a paired Student’s t-tests with p<0.05 considered significant. Addition of histamine (100µM) increased tonic contractions in juvenile U&LP by 47.84±6.52 mN/g (p<0.001, n=51) and in adult U&LP by 50.76±4.10 mN/g (p<0.001, n=55). Additionally, the frequency of phasic spontaneous contractions increased by 1.29±0.26 cpm (p<0.001, n=51) in juvenile tissues and by 1.18±0.16 cpm (p<0.001, n=55) in adult. The amplitude of phasic contraction decreased by 5.54±1.60 mN/g (p<0.001, n=51) in juvenile tissues and by 10.05±2.06 mN/g (p<0.001, n=55) in adult. In detrusor preparations, juveniles showed significantly greater (p < 0.05) increases in tonic contractions of 19.10±4.92 mN/g (n=51) when compared to adult tissues exhibiting increases of 8.21±0.89 mN/g (n=56) to histamine (100 µM). In the presence of H1 antagonists, increases in tonic contractions and phasic activity to histamine (100µM) were significantly inhibited in both juvenile (p<0.05 for all) and adult (p<0.05) tissues. Treatment with H2 antagonist in U&LP of juvenile tissues caused significant enhancement of tonic contractions when compared to control tissues (p<0.05). These increases were not observed in adult U&LP and detrusor of both juvenile and adult tissues. Treatment with H3 and H4 antagonist did not influence contractile responses to histamine (100µM) in the U&LP and detrusor of both age groups. In conclusion, histamine and PGE2 increases the contractile activity of both U&LP and detrusor in juvenile and adult animal models. There was no difference in the contractile responses observed to histamine in the U&LP of juvenile and adult tissues. However, maximal contractions in detrusor were greater in juvenile tissues than in adult samples. The activation of the H2 receptor inhibited tonic contractions in the U&LP of juvenile animals but did not affect adult U&LP or the contractility of detrusor in both age groups. There were no differences in contractile responses in both U&LP and detrusor in response to PGE2 between juvenile and adult tissues. These results suggest that any influence of the inflammatory mediator histamine on the increased prevalence of bladder dysfunction observed in ageing may be related to its influence on the detrusor smooth muscle.
Future Physiology 2020 (Virutal) (2020) Proc Physiol Soc 46, PC0077
Poster Communications: Inflammatory mediators as contributors to age-related urinary bladder dysfunction
Zane Stromberga1, Russ Chess-Williams1, Christian Moro1
1 Bond University, Gold Coast, Australia
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Where applicable, experiments conform with Society ethical requirements.