Effect of age on the responses of rat bladder detrusor strips to adenosinetriphosphate

Objective To assess age-related changes in bladder function using the contr actile responses to ATP of detrusor strips from rats of various ages. Materials and methods Urinary bladders were obtained from male Wistar rats aged 9 weeks (young), 24 weeks (adult) and 24 months (aged). Contractions o f urinary bladder muscle strips to ATP were measured isometrically. The siz e of the initial phasic response and the secondary contractile response tha t developed after washing out ATP (postwashout contraction) were measured. The magnitudes of the ATP-induced phasic and postwashout contraction were c ompared among the age groups. During the contractions, prostanoid concentra tions in the organ-bath medium were measured using an enzyme immunoassay. Results The ATP-induced postwashout contraction did not occur after stimula tion with KCl or acetylcholine, but was induced by alpha,beta-methylene ATP . Both the phasic and postwashout contractions were concentration-dependent . Although the phasic contraction did not change progressively with age, th e magnitude and duration of the postwashout contraction increased substanti ally with age. Nicardipine (a calcium antagonist) slightly inhibited both c ontractions. Suramin (a nonselective P2-receptor antagonist) did not signif icantly inhibit the phasic contraction, but reduced the postwashout contrac tion. PPADS (a selective P2X receptor antagonist) did not inhibit either co ntraction. Indomethacin (a prostaglandin synthesis inhibitor) had no effect on the phasic contraction but almost completely blocked the postwashout co ntraction when added before ATP stimulation, but was less effective when ad ded after ATP. The prostaglandin E2 concentration in the organ bath increas ed during the postwashout contraction. Conclusions These findings suggest that the ATP-induced postwashout contrac tion is not directly mediated by P2x purinoceptors, but results from the sy nthesis of prostaglandins, especially E2, which is a sensory autacoid. The age-linked increase in postwashout contraction may be involved in the chang es in sensory and voiding mechanisms seen in the aged urinary bladder.