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Keywords:

  • Angiotensin II;
  • detrusor;
  • autoradiography;
  • losartan;
  • PD 123319

Objectives To investigate the receptors for angiotensin II (AII, reported to be a potent contractile agent in human urinary bladder), using functional and autoradiographic techniques in child and adult bladder specimens.

Materials and methods Bladder specimens were obtained from 61 children (aged 4 months to 12 years) undergoing ureteric reimplantation for vesico-ureteric reflux, and from 10 adults undergoing cystectomy. After overnight storage, the mucosa was removed and isometric contractions obtained from detrusor muscle strips in the presence of phosphoramidon (10 µmol/L). Only one concentration of AII was added to each preparation because of tachyphylaxis. The response to KCl (124 mmol/L) was 43% of that to carbachol (100 µmol/L). Sections of child bladder were radio-labelled with the ligand [125I]Sar1,Ile8-AII and binding sites visualized using emulsion autoradio- graphy.

Results The potency of AII was similar in child and adult detrusor strips, with mean ( sem) pD2 values of 6.9 (1.0) (n = 25) and 6.7 (0.2) (n = 9) respectively, and the maximum responses (to 10 µmol/L AII) rather low (39% and 49%, respectively, P > 0.05), compared with carbachol (100 µmol/L). There were no age- or gender-related differences. Responses to AII in strips from children under 3 years old were antagonized by the AT1 receptor antagonist losartan (1 µmol/L) but not by the AT2 receptor antagonist PD 123319 (1 µmol/L), indicating interaction with the AT1 receptor. Sections of child bladder radiolabelled with [125I]Sar1,Ile8-AII showed moderate specific binding over detrusor muscle and arterioles, with denser specific binding over subepithelial blood vessels. Specific binding was inhibited by co-incubation with losartan (10 µmol/L) but not with PD 123319 (10 µmol/L).

Conclusion AII was a weak contractile agent of detrusor strips, with no significant differences in potency between child and adult bladder samples. These data show the presence of functional AT1 but not AT2 receptors in child detrusor smooth muscle.