Nephrotoxicity of angiotensin inhibition during the perinatal period

As the only ex utero mechanism for the removal of nitrogenous waste, the ma mmalian kidney achieves some 50-fold increase in urine production during th e perinatal period when the placental circulation becomes no longer availab le as a functional dialyzer, This urine is efficiently removed from the kid ney by the renal pelvis, a smooth muscle structure unique to mammals, which develops during the perinatal period. We found that mutant mice completely devoid of angiotensinogen or its type 1 receptor, as well as wild-type neo nates given an ACE inhibitor, fail to develop a renal pelvis or a ureteral peristaltic movement. These structural and functional defects in the urinar y tract are followed by severe obstructive injury of the renal parenchyma. The ability of angiotensin to directly induce the pelvis is demonstrated in an organ culture system, in which treatment with angiotensin induces the c haracteristic smooth muscle layer in the wild type, but not in homozygous n ull mutants. Upregulation of both renal angiotensin content and type 1 rece ptor at the renal hilum are also demonstrated in the wild type during the t ransition from intra- to extra-uterine life. By inducing the timely develop ment of the renal pelvis, angiotensin thus facilitates the removal from the renal parenchyma of the urine that promptly increases at birth, thereby ef fectively preventing a buildup of intrarenal pressure and a consequent deve lopment of dysmorphic kidney. Copyright (C) 2000 S. Karger AG, Basel.