Angiotensin induces the urinary peristaltic machinery during the perinatal period.

Abstract

The embryonic development of mammalian kidneys is completed during the perinatal period with a dramatic increase in urine production, as the burden of eliminating nitrogenous metabolic waste shifts from the placenta to the kidney. This urine is normally removed by peristaltic contraction of the renal pelvis, a smooth muscle structure unique to placental mammals. Mutant mice completely lacking angiotensin type 1 receptor genes do not develop a renal pelvis, resulting in the buildup of urine and progressive kidney damage. In mutants the ureteral smooth muscle layer is hypoplastic and lacks peristaltic movements. We show that angiotensin can induce the ureteral smooth muscles in organ cultures of wild-type, but not mutant, ureteral tissues and that, in wild-type mice, expression of both renal angiotensin and the receptor are transiently upregulated at the renal outlet at birth. These results reveal a new role for angiotensin in the unique cellular adaptations of the mammalian kidney to the physiological stresses of postnatal life. ( J.

What Have We Learned from Gene Targeting Studies for the Renin Angiotensin System of the Kidney?

“…Mutant mice completely lacking Agtrl genes do not develop a renal pelvis, resulting in a buildup of urine, papillary atrophy, and progressive kidney damage. In the mutants, the ureteral smooth muscle layer is hypoplastic and lacks peristaltic movements (57). These results reveal a newrole for AngII in the unique cellular adaptations of the mammaliankidney to the physiological stress of the postnatal life.…”

Development of the kidney medulla

“…The mechanisms that have been implicated in functional ureteral obstruction in these mice include defective ureteral peristalsis (failure of ureteral peristalsis to propagate in a sequential proximal-distal direction), reduced number of ureteral pacemaker cells and decreased proliferation of periureteral mesenchymal cells. 76,77 Although medullary hypoplasia and hydronephrosis observed in angiotensin (Ang) II AT1 receptor (AT1R)-deficient mice may result from impaired ureteral peristalsis due to hypoplastic ureteral smooth muscle layer, 78 our previous studies suggest that aberrant branching morphogenesis of the UB may also contribute to medullary defects observed in these mutants. 79 The possibility that medullary hypoplasia may be due in some cases to an intrinsic defect in medullary morphogenesis, rather than to urinary tract obstruction, is supported by the findings that Wnt7b-and Adamts 1/4-or Esrrg-null mice exhibit hypoplastic renal medulla at birth in the absence of structural abnormalities of the lower urinary tract.…”

Cell Biology of Ureter Development

“…These events are mediated by the protein phosphatase, calcineurin, 58 and by AngII signaling. 59 Mice genetically engineered to lack key molecules in the ureteric SM-differentiation pathway have the common phenotype of hydroureter/ hydronephrosis. This arises not from anatomic obstruction but because of a backup of urine in a functionally obstructed tube lacking normal peristaltic waves.…”