Multiple physiological adaptations must occur in placental mammals at birth when the fetus switches from dependence on a maternal life support system to a free living existence. The renal system, in particular, faces the dual challenges of achieving a rapid some 50-fold increase in urine production to eliminate nitrogenous wastes now entirely through the kidney, and at the same time, of establishing a mechanism by which the high urine production is matched by efficient removal of urine from the kidney. The latter is accomplished by development of the pelvis, an organ unique to mammals, which, under the control of its pacemaker cells, initiates the peristaltic movement to rapidly transfer urine from the kidney to the ureter.

Here, we report that mice lacking functional genes for both the angiotensin type 1A and 1B receptors do not develope a renal pelvis nor peristaltic movements of the ureter after birth. These defects are followed by severe obstructive injury of the renal parenchyma. In mutants, the ureteral muscle layer is also hypoplastic. Angiotensin can induce the muscle layer prematurely in organ cultures of ureteral tissues from wild type but not mutant embryos. Timely transient upregulations of both renal angiotensin and the type 1 receptor at the renal hilum are demonstrated at birth in wild type mice. Thus, these ontogenic regulations are synchronized with the dramatic increase in urine output characteric of mammals at birth. The angiotensin-type 1 receptor system induces in a timely fashion at birth the machinery, i.e. the pelvis, that removes urine promptly and constantly from the renal parenchyma by peristalsis to prevent build-up of high intrarenal pressure that is extremely harmful for the kidney. The results impart physiological significance to the upregulation of renin-angiotensin system that occurs at birth and during urinary tract obstruction, teleology of which has long been debated.