Ureteric bud derivatives express angiotensinogen and AT(1) receptors

Inactivation of the renin-angiotensin system interferes with the morphogene sis of the renal medulla. Thus ureteric bud (UB) derivatives may be a targe t for angiotensin production and action. To begin to test this hypothesis, we examined the cellular expression of angiotensinogen (Ao) and AT(1) recep tor proteins during rat metanephrogenesis by immunohistochemistry. In addit ion, we tested whether UB-derived cells in culture express the Ao and AT(1) proteins. On embryonic day E15, Ao and AT(1) are expressed in the UB branc hes and stromal mesenchyme. S-shaped bodies, including the vascular cleft, express AT(1) but not Ao. The metanephric mesenchyme and pretubular aggrega tes are Ao negative and AT(1) negative. Expression of Ao and AT(1) in UB br anches and ampullae is also observed on E16. However, UB expression of Ao i s transient and is no longer detectable in the developing distal nephron be yond E17. On E17, both Ao and AT(1) are expressed in capillary loop glomeru li and proximal tubules, whereas UB branches express AT(1) only. By E18, th e majority of Ao immunoreactivity is clustered in terminally differentiated proximal tubules, whereas AT(1) receptors are expressed in both proximal a nd distal nephron segments. The specificity of Ao and AT(1) staining was do cumented by the elimination/attenuation of immunoreactivity after preadsorp tion of the primary antibodies with their respective antigens. Consistent w ith the in vivo findings, the AT(1) protein is abundantly expressed in cell ular lysates of mouse UB (E11.5) and IMCD3 (adult) cells. Moreover, AT(1) r eceptors in UB and IMCD3 cells are functional, since angiotensin II treatme nt elicits the tyrosine phosphorylation of the mitogen-activated protein ki nases, ERK1/2. To our knowledge, this is the first demonstration of Ao and AT(1) protein expression in the developing distal nephron. Angiotensin II m ay have a paracrine role in the ontogeny of the collecting system.