In vitro contractile responses of detrusor to carbachol and neurokinin A, in children with recurrent urinary tract infection or day wetting

Abstract

Objective To investigate whether a history of recurrent urinary tract infection (UTI) and/or the presence of day-wetting/urge symptoms might in¯uence the contractile responses to the cholinergic agonist carbachol or to the sensory neuropeptide neurokinin A (NKA) in the urinary bladder in children. Patients and methods Small detrusor strips were taken from the margin of the cystotomy incision of the bladder dome during surgery to correct vesico-ureteric re¯ux (VUR) in 62 children (aged 4 months to 12 years) or for unrelated bladder conditions in ®ve controls (aged 3 months to 13 years). Concentrationresponse curves to carbachol and NKA were constructed using organ-bath techniques, and results compared for age, sex, weight of the detrusor strip, UTI history or day-wetting syndrome. Results The contractile responses to NKA were no different for any of the features investigated. The contractile response to carbachol and NKA in detrusor from control and VUR patients was not signi®cantly different. The children with a history of UTI were signi®cantly older than those without. The contractility in response to carbachol was greater in older girls (aged 4±12 years) than younger girls (<4 years) and than in all boys (<4 years and 4±12 years; ANOVA P = 0.013). The mean (SEM) maximum contractile response to carbachol in the group of 20 young children (4±30 months) with previous UTI was 3.0 (0.3) g, whereas the maximum response in the age-matched group of 11 without UTI was 1.8 (0.3) g (P = 0.046). There were no signi®cant differences in maximum responses between those with day-wetting and those without (aged >4 years), although there was a signi®cant difference in pD 2 value, at 6.19 (0.13) and 5.58 (0.14), respectively (P = 0.018). Conclusion Carbachol produced a larger contractile response in detrusor from children with a history of UTI than from those without, indicating possible alterations in muscarinic receptor characteristics. An increased sensitivity to muscarinic stimulation in daywetting children was also suggested, whereas NKA is unlikely to be involved in any of these pathophysiological conditions.

Loss of Purinergic P2X3and P2X5Receptor Innervation in Human Detrusor from Adults with Urge Incontinence

“…Infant bladder specimens were taken at cystotomy during surgical correction of vesicoureteric reflux that was detected by antenatal ultrasonography with neonatal follow-up, or by sibling tracing. All subjects demonstrated radiological grade III-IV reflux (Lebowitz et al, 1985) and had failed to resolve spontaneously with antibiotic prophylaxis, as previously reported (Werkstrom et al, 2000); urine culture was sterile before surgery. C ystoscopic biopsies were taken from patients with proven idiopathic detrusor instability (as per urodynamic testing) who had failed to respond to antimuscarinic drugs for Ͼ12 months (Moore et al, 1992).…”

Angiotensin II in child urinary bladder: functional and autoradiographic studies

“…These ®ndings are unlikely to be affected by the children having VUR, because our previous study using similar specimens showed no difference in responses to either carbachol or neurokinin A compared to control specimens [18]. Despite the many specimens there were relatively few observations, because the problem of tachyphylaxis with AII permitted only one response from each strip.…”

Muscarinic receptors of the urinary bladder: detrusor, urothelial and prejunctional

“…Reducing oestrogen levels by ova rectomizing rats reduces detrusor sensitivity to cholinergic stimulation whilst oestrogen supplementation increases bladder responses (Palea & Angel, 1997). These findings may explain the differences in detrusor contractility observed in children; responses in girls being greater than those observed in boys (Werkstrom et al , 2000). Whether these differences exist in the adult are uncertain particularly as the effects of oestrogen are age dependent, for example, in the aged rat, muscarinic responses are depressed because of blunted calcium entry (Yu et al , 1997), yet mature rats may be more sensitive to oestrogen (Diep & Constantinou, 1999).…”

“…The sensitivity of the detrusor muscle to muscarinic agonists is enhanced in several diseased states including diabetes (Mimata et al , 1995; Kanda et al , 1997), denervation (Braverman, Luthin & Ruggieri, 1998b), bladder outflow obstruction (Speakman et al , 1987), chronic alcohol intake (Knight, Brizzolara, Soediono, Karoon & Burnstock, 1995) and ageing (Yu, Wein & Levin, 1997). In children with recurrent urinary tract infections there is a selective increase in bladder sensitivity to carbachol while responses to neurokinin A are unaffected (Werkstrom et al , 2000). It has been suggested that chronic bladder outlet obstruction also causes a supersensitivity of the detrusor muscle because of a resulting parasympathetic denervation (Harrison, Hunnam, Farman, Ferguson & Doyle, 1987; Speakman et al , 1987).…”