Angiotensin II in child urinary bladder: functional and autoradiographic studies

Objectives To investigate the receptors for angiotensin II (AII, reported t o 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 (age d 4 months to 12 years) undergoing ureteric reimplantation for vesico-urete ric reflux, and from 10 adults undergoing cystectomy. After overnight stora ge, the mucosa was removed and isometric contractions obtained from detruso r muscle strips in the presence of phosphoramidon (10 mu mol/L). Only one c oncentration of AII was added to each preparation because of tachyphylaxis. The response to KCl (124 mmol/L) was 43% of that to carbachol (100 mu mol/ L). Sections of child bladder were radio-labelled with the ligand [I-125]Sa r(1),Ile(8)-AII and binding sites visualized using emulsion autoradio- grap hy. Results The potency of AII was similar in child and adult detrusor strips, with mean (sem) pD(2) values of 6.9 (1.0) (n = 25) and 6.7 (0.2) (n = 9) re spectively, and the maximum responses (to 10 mu mol/L AII) rather low (39% and 49%, respectively, P > 0.05), compared with carbachol (100 mu mol/L). T here were no age- or gender-related differences. Responses to AII in strips from children under 3 years old were antagonized by the AT(1) receptor ant agonist losartan (1 mu mol/L) but not by the AT(2) receptor antagonist PD 1 23319 (1 mu mol/L), indicating interaction with the AT(1) receptor. Section s of child bladder radiolabelled with [I-125]Sar(1),Ile(8)-AII showed moder ate specific binding over detrusor muscle and arterioles, with denser speci fic binding over subepithelial blood vessels. Specific binding was inhibite d by co-incubation with losartan (10 mu mol/L) but not with PD 123319 (10 m u mol/L). Conclusion AII was a weak contractile agent of detrusor strips, with no sig nificant differences in potency between child and adult bladder samples. Th ese data show the presence of functional AT(1) but not AT(2) receptors in c hild detrusor smooth muscle.